Eduovisual
Endocrine
Graves disease: management and pregnancy considerations
— Female:male ratio ~5–10:1; peak incidence ages 30–50, but can occur at any age including pregnancy and adolescence
— Strong genetic predisposition: HLA-DR3, CTLA-4, PTPN22; clusters with type 1 diabetes, vitiligo, pernicious anemia, celiac, Addison disease (polyglandular autoimmunity)
— Triggers: postpartum state (peak 3–6 months postpartum), high iodine load, stress, smoking (also worsens orbitopathy), recent interferon-α, alemtuzumab, or immune checkpoint inhibitor therapy
— Triad: hyperthyroidism + diffuse non-tender goiter + orbitopathy (proptosis, lid lag, periorbital edema) ± pretibial myxedema or thyroid acropachy
— Unexplained sinus tachycardia, atrial fibrillation in a younger patient, weight loss with increased appetite, anxiety, tremor, heat intolerance, insomnia, oligomenorrhea, frequent stools
— Elderly: often "apathetic hyperthyroidism" — weight loss, depression, new AF, CHF without classic adrenergic symptoms
Board pearl: A young woman with proptosis + suppressed TSH + diffuse goiter with a bruit essentially clinches Graves — TRAb confirms but is not always required if the clinical picture is classic. If the picture is atypical (nodular gland, painful gland, recent iodine load, postpartum), order TRAb and/or radioactive iodine uptake before committing to definitive therapy.
— Weight loss despite increased appetite, heat intolerance, diaphoresis, fine tremor
— Palpitations, exertional dyspnea, reduced exercise tolerance; new-onset atrial fibrillation (10–15% of overt hyperthyroid adults)
— Anxiety, irritability, emotional lability, insomnia, difficulty concentrating ("hyperthyroid pseudo-ADHD")
— Hyperdefecation or frank diarrhea (not malabsorption), proximal muscle weakness (climbing stairs, rising from chair)
— Oligomenorrhea or amenorrhea, decreased libido, gynecomastia in men, subfertility
— Thyroid eye disease (TED/orbitopathy) in ~25–50%: grittiness, retrobulbar pressure, diplopia, proptosis, lid retraction; can predate, parallel, or follow hyperthyroidism
— Pretibial myxedema (1–4%): non-pitting, orange-peel plaques over shins
— Thyroid acropachy (<1%): digital clubbing + periosteal reaction — pathognomonic
— Pregnancy status / LMP / contraception — changes entire management algorithm
— Iodine exposure: recent CT contrast, amiodarone, kelp supplements (suggests iodine-induced thyrotoxicosis instead)
— Neck pain or recent viral illness (subacute thyroiditis differential)
— Postpartum status (postpartum thyroiditis vs. postpartum Graves flare)
— Smoking — independent risk factor for TED progression; counseling is mandatory
— Family history of autoimmune thyroid, T1DM, vitiligo
— Medication review: lithium, amiodarone, checkpoint inhibitors, biotin (interferes with TFT immunoassays — hold 48–72h before testing)
Key distinction: Painful tender goiter with elevated ESR and low RAIU = subacute (de Quervain) thyroiditis, not Graves. Painless postpartum thyrotoxicosis with low RAIU = postpartum thyroiditis. Graves uptake is diffusely elevated. Always anchor on uptake when the clinical picture is muddy.
— Resting tachycardia (sinus or AF), widened pulse pressure, systolic hypertension
— Low-grade temperature elevation; in thyroid storm, T >38.5°C, HR often >140, AMS, CHF signs
— Orthostatics may reveal high-output state; check for signs of decompensated heart failure (JVD, S3, rales, edema) — high-output failure can occur, especially in elderly or those with underlying cardiac disease
— Warm, moist, velvety skin; palmar erythema; onycholysis (Plummer nails)
— Fine resting tremor of outstretched hands (place paper on hand)
— Pretibial myxedema — bilateral non-pitting, peau d'orange plaques
— Proximal muscle weakness (sit-to-stand without arms)
— Diffusely enlarged, smooth, non-tender, rubbery goiter; auscultate for a thyroid bruit (highly specific for Graves — reflects hypervascularity)
— Key distinction: nodular or asymmetric gland suggests toxic multinodular goiter or toxic adenoma; tender gland suggests subacute thyroiditis
— Lid lag (von Graefe) and lid retraction (Dalrymple) = adrenergic effects, seen in any hyperthyroidism
— True orbitopathy (Graves-specific): proptosis (measure with Hertel exophthalmometer; abnormal >20–22 mm), conjunctival injection/chemosis, periorbital edema, restricted extraocular movements (especially upgaze), diplopia, optic nerve compression (decreased color vision, RAPD, decreased acuity)
— Use the CAS (Clinical Activity Score): ≥3/7 indicates active TED warranting referral
— Hyperdynamic precordium, loud S1, midsystolic flow murmur; irregular irregular rhythm if AF
— Auscultate lungs for evidence of decompensation
Step 3 management: Any patient with decreased visual acuity, color desaturation, or corneal exposure is a same-day ophthalmology emergency — do not wait for outpatient referral. IV glucocorticoids and possible orbital decompression are time-sensitive.
— TSH (suppressed, typically <0.01 mIU/L in overt Graves)
— Free T4 and free T3 (or total T3) — elevated; isolated T3 toxicosis can occur early in Graves or in toxic adenoma
— Subclinical hyperthyroidism: low TSH, normal FT4/FT3 — still warrants evaluation if persistent, especially TSH <0.1 or age >65 (AF and osteoporosis risk)
— TRAb (TSH receptor antibody) or TSI (thyroid-stimulating immunoglobulin): sensitivity ~95–99% for Graves; preferred in pregnancy (avoids radiation) and when RAIU is contraindicated
— Radioactive iodine uptake and scan (RAIU/scan): diffusely elevated uptake (usually >35% at 24h) confirms Graves; "hot nodule" with suppressed surrounding tissue = toxic adenoma; patchy uptake = toxic MNG; near-zero uptake = thyroiditis, exogenous thyroid hormone, or iodine load
— Anti-TPO and anti-Tg: often positive in Graves but nonspecific (also Hashimoto)
— CBC (mild normocytic anemia, occasional leukopenia — baseline before methimazole)
— CMP (mild transaminitis common; baseline before thionamides; mild hypercalcemia from bone resorption)
— Pregnancy test (β-hCG) in any reproductive-age woman — mandatory before RAI or scan
— ECG — sinus tach, AF, LVH
— Lipid panel (often paradoxically low LDL/total cholesterol)
— Biotin (>5 mg/day, hair/nail supplements) causes falsely low TSH and falsely high FT4/FT3/TRAb in many immunoassays — hold ≥48–72h before drawing
— Heterophile antibodies, severe nonthyroidal illness, and amiodarone confound interpretation
CCS pearl: Order TSH + FT4 + FT3 + TRAb + β-hCG together at first visit. If TRAb is positive and presentation is classic, you can skip RAIU and proceed to definitive treatment counseling — saves a visit and radiation exposure.
— Thyroid ultrasound with color Doppler: diffusely enlarged, hypoechoic, hypervascular ("thyroid inferno") gland — useful when RAIU is contraindicated (pregnancy, breastfeeding, recent iodine load) or when nodules are palpated
— Any dominant or suspicious nodule ≥1 cm in a Graves gland → evaluate per ATA nodule guidelines; FNA if TI-RADS criteria met (Graves patients have slightly higher risk of thyroid cancer in coexisting nodules)
— Orbital MRI or CT for moderate-to-severe TED: enlarged extraocular muscles (sparing tendons), increased orbital fat, apical crowding suggesting optic nerve compression
— TRAb >3× ULN in pregnancy at any point predicts fetal/neonatal hyperthyroidism via transplacental antibody passage — mandates fetal surveillance
— TRAb is also useful to predict remission after antithyroid drug (ATD) course: persistently elevated at 12–18 months → low remission likelihood
— Amiodarone-induced thyrotoxicosis: distinguish Type 1 (iodine-induced, underlying nodular disease, increased Doppler flow) vs. Type 2 (destructive thyroiditis, decreased flow). Type 1 → thionamides ± perchlorate; Type 2 → glucocorticoids
— TSH-secreting pituitary adenoma (rare): inappropriately normal/elevated TSH with high FT4 → pituitary MRI, α-subunit
— Trophoblastic disease / hyperemesis gravidarum: β-hCG cross-stimulates TSH receptor → transient gestational thyrotoxicosis; TRAb negative; RAIU contraindicated
— Baseline CBC, LFTs, TFTs before thionamides
— Counsel on contraception before RAI (avoid pregnancy 6 months post-RAI in women, 3–4 months in men)
— Pre-thyroidectomy: ENT consult, vocal cord exam, calcium/vitamin D optimization, render euthyroid with thionamide + KI for 10–14 days preop
Board pearl: Low RAIU thyrotoxicosis differential = TIPSEE: Thyroiditis (subacute, postpartum, silent), Iodine load, Pills (exogenous levothyroxine — factitious), Struma ovarii, Excess hCG, Extra-thyroidal (metastatic functioning thyroid cancer).
— Antithyroid drugs (ATDs): methimazole (preferred) or PTU
— Radioactive iodine (RAI) ablation
— Total or near-total thyroidectomy
— First episode, mild disease, small goiter, low TRAb titer (higher remission chance, ~40–50% at 12–18 months)
— Pregnancy or planning pregnancy within 6 months
— Active moderate-severe TED (RAI can worsen orbitopathy; if RAI chosen, give prophylactic prednisone)
— Patient preference to avoid permanent hypothyroidism
— Children and adolescents (often first-line)
— Recurrence after ATD course, contraindications to surgery, large goiter without compression, no significant TED, no pregnancy planning within 6–12 months
— Older patients with cardiac comorbidities (definitive, low procedural risk)
— Contraindications: pregnancy, breastfeeding, active moderate-severe TED, suspicion of thyroid malignancy, inability to follow radiation precautions
— Very large goiter (>80 g) with compressive symptoms, coexisting suspicious nodule or thyroid cancer, moderate-severe active TED, pregnancy with ATD intolerance (perform in 2nd trimester), need for rapid resolution, patient preference
— Requires experienced high-volume surgeon (>25 thyroidectomies/year) to minimize recurrent laryngeal nerve injury and hypoparathyroidism
— β-blockers (atenolol 25–50 mg daily or propranolol 10–40 mg q6–8h) for HR control, tremor, anxiety — start at first visit while awaiting definitive plan
— Propranolol additionally blocks peripheral T4→T3 conversion at high doses
Step 3 management: Start a β-blocker the same day for any symptomatic patient with HR >90, then layer thionamide once you've drawn baseline CBC/LFTs. Don't wait for RAIU results in a classic Graves presentation with positive TRAb.
— Dosing: mild (FT4 1–1.5× ULN) 5–10 mg/day; moderate (1.5–2×) 10–20 mg/day; severe (>2–3×) 20–40 mg/day; single daily dose acceptable
— Onset of euthyroidism: 4–8 weeks; titrate based on FT4 and FT3 (TSH stays suppressed for months — don't dose by TSH early)
— Two strategies: titration (preferred, lower side effects) or block-and-replace (high-dose MMI + levothyroxine — rarely used except in pregnancy with TRAb-driven fetal risk)
— Duration: 12–18 months, then trial discontinuation if TRAb has normalized and patient is euthyroid on low dose
— Indications: first trimester of pregnancy (lower teratogenicity than MMI), thyroid storm (blocks peripheral T4→T3 conversion), MMI intolerance
— Dosing: 50–150 mg PO q8h; storm: 200 mg q4h
— Black box: hepatotoxicity (fulminant hepatic failure, 1 in 10,000), more severe than MMI cholestasis
— Agranulocytosis (0.2–0.5%): sudden fever, sore throat, mouth ulcers → stop drug, get CBC immediately, do NOT switch to the other thionamide (cross-reactivity)
— Hepatotoxicity: MMI → cholestatic; PTU → hepatocellular necrosis. Check LFTs at baseline and if symptomatic
— Rash (5%), arthralgia, ANCA-associated vasculitis (PTU > MMI), lupus-like syndrome
— MMI teratogenicity: aplasia cutis, choanal/esophageal atresia, omphalocele (highest risk weeks 6–10)
— TFTs every 4–6 weeks until euthyroid, then every 2–3 months
— Routine CBC/LFT monitoring is not recommended (low yield) — instead, instruct patient to seek care for warning symptoms
Board pearl: PTU in 1st trimester → switch to MMI at start of 2nd trimester (after organogenesis) to minimize cumulative hepatotoxicity risk while still avoiding MMI's worst teratogenic window.
— Single oral dose, typically 10–15 mCi (or calculated based on gland size and uptake)
— Mechanism: β-emission destroys follicular cells; clinical effect over 6–18 weeks
— Pre-RAI prep: stop MMI 3–5 days before; restart if needed 3–7 days after; β-blocker continued; low-iodine diet 1–2 weeks prior
— Pretreat with prednisone (0.3–0.5 mg/kg, taper over 6–12 weeks) if mild TED present or risk factors (smoker, high TRAb, recent severe hyperthyroidism)
— Outcome: >80% become hypothyroid within 1 year — this is the goal, not a complication; start levothyroxine when FT4 drops below normal
— Radiation precautions: avoid close contact with children/pregnant women for 3–7 days; no pregnancy for 6 months (women) or 3–4 months (men, due to spermatogenesis)
— Contraindications: pregnancy, breastfeeding (must stop ≥6 weeks before), active moderate-severe TED, inability to follow precautions
— Indications recap: large compressive goiter, coexisting cancer suspicion, severe active TED, pregnancy with ATD failure/allergy (2nd trimester optimal), patient preference
— Preop: render euthyroid with MMI (4–8 weeks); add SSKI/Lugol's iodine 5–7 drops TID for 10–14 days preop to reduce gland vascularity (Wolff-Chaikoff effect); β-blocker continued
— Complications: recurrent laryngeal nerve injury (1–2%), permanent hypoparathyroidism (1–3%), hematoma (airway emergency), hypothyroidism (100% — intentional)
— Postop: start levothyroxine ~1.6 µg/kg/day the next day; check calcium/PTH q6h initially; discharge with calcium + calcitriol if hypocalcemic
CCS pearl: For thyroidectomy on the CCS, order: ENT preop laryngoscopy, MMI continued, SSKI started 10 days preop, β-blocker, type & screen, baseline calcium/PTH/vit D. Postop orders: levothyroxine, ionized calcium q6h, drain output check, voice assessment.
— Often apathetic hyperthyroidism: weight loss, depression, weakness, AF, CHF without classic adrenergic surge — low threshold for TSH screening in unexplained AF or weight loss
— Higher prevalence of subclinical hyperthyroidism; treat if TSH <0.1 mIU/L persistently (AF risk doubles, fracture risk increases ~30%, dementia association)
— RAI is often preferred: definitive, single dose, lower surgical risk; counsel on transient post-RAI thyrotoxicosis flare and pretreat fragile cardiac patients with ATDs first to deplete hormone stores
— β-blocker selection: atenolol or metoprolol (cardioselective) preferred in COPD; caution with decompensated HF — use IV esmolol in storm, but β-blockade may be essential to control rate-related cardiomyopathy
— Bone health: DEXA at diagnosis; ensure calcium/vitamin D; treat osteoporosis aggressively — hyperthyroidism accelerates bone loss
— Drug-drug: warfarin INR rises in thyrotoxicosis (decreases as patient becomes euthyroid — recheck frequently); digoxin clearance increased
— Rate control with β-blocker; CCB if β-blocker contraindicated
— Anticoagulation: apply CHA₂DS₂-VASc as usual; hyperthyroidism alone is not an automatic indication but threshold to anticoagulate is low given embolism risk
— ~60% convert spontaneously to sinus rhythm within 4 months of euthyroidism; delay elective cardioversion until euthyroid if stable
— Avoid PTU (hepatotoxicity); MMI preferred. Reduce MMI dose and monitor LFTs closely
— Baseline LFTs mandatory; hold thionamide if ALT >3× ULN
— Thionamides do not require renal dose adjustment
— Atenolol is renally cleared — use metoprolol or propranolol if CKD 4–5
— RAI dosing unchanged but radiation precautions extended in dialysis
Step 3 management: In an 78-year-old with new AF and weight loss → check TSH. If suppressed with positive TRAb → start β-blocker, methimazole, anticoagulate per CHA₂DS₂-VASc, refer for RAI as definitive therapy once stabilized. Avoid amiodarone for rhythm control.
— Women on MMI planning pregnancy: switch to PTU before conception or as soon as pregnancy confirmed (within first weeks); alternatively, achieve definitive cure (RAI ≥6 months pre-pregnancy or thyroidectomy) before conceiving
— Discuss contraception during ATD use given teratogenic concerns
— 1st trimester: PTU 50–150 mg q8h (minimize MMI teratogenic risk weeks 6–10)
— 2nd trimester onward: switch to MMI (lower maternal hepatotoxicity)
— Goal: maintain FT4 at or just above the upper limit of normal using the lowest effective ATD dose — overtreatment causes fetal hypothyroidism/goiter
— Check TFTs every 2–4 weeks initially, then every 4–6 weeks once stable
— Avoid block-and-replace (levothyroxine doesn't cross placenta well; ATDs do — fetus would become hypothyroid)
— TRAb at initial visit and at 18–22 and 30–34 weeks: if >3× ULN, arrange fetal surveillance (US for goiter, growth, HR, hydrops) by maternal-fetal medicine
— β-blockers: short-term propranolol or labetalol acceptable; avoid prolonged use (IUGR, neonatal hypoglycemia, bradycardia)
— RAI absolutely contraindicated; thyroidectomy reserved for ATD failure/allergy and ideally performed in 2nd trimester
— Graves often flares 3–6 months postpartum — reassess TFTs
— Breastfeeding: both MMI (≤20 mg/day) and PTU (≤450 mg/day) are compatible — preferred MMI; dose after feeds
— Distinguish from postpartum thyroiditis (low RAIU, self-limited, TPO+, no TRAb)
— Maternal TRAb crosses placenta → neonatal Graves (transient, weeks to months); screen at birth and again at days 3–5 and 10–14
— MMI is first-line (PTU avoided due to hepatotoxicity except in storm or MMI allergy)
— Longer ATD courses (often 2–4 years) given lower remission rates
— Definitive therapy preferred for relapse: RAI generally avoided <5 years old; thyroidectomy at experienced center
Board pearl: "Pregnant, hyperthyroid, MMI" → switch to PTU" in 1st trimester. "3rd trimester, MMI" → continue MMI. "Pregnant, needs RAI" → never; consider thyroidectomy in 2nd trimester.
— Precipitants: surgery, infection, trauma, parturition, RAI, iodinated contrast, abrupt thionamide cessation, DKA
— Diagnosis: Burch-Wartofsky score ≥45 (fever, CNS dysfunction, GI/hepatic, CV, AF, CHF) — clinical, not lab-based
— Treatment bundle (order matters): PTU 500–1000 mg load then 250 mg q4h → iodine (SSKI/Lugol's) 1 hour AFTER PTU (giving iodine first fuels hormone synthesis) → propranolol 60–80 mg q4h or IV esmolol → hydrocortisone 100 mg IV q8h (blocks T4→T3, treats relative adrenal insufficiency) → cooling, fluids, treat trigger
— Atrial fibrillation (10–15%), high-output heart failure, thyrotoxic cardiomyopathy, exacerbation of CAD/angina, increased VTE risk
— Accelerated bone loss, osteoporosis, fragility fractures — especially postmenopausal women
— Mild (lid retraction, dry eye) → lubricants, prisms
— Moderate-severe active → IV methylprednisolone weekly pulses (cumulative 4.5 g over 12 weeks); teprotumumab (IGF-1R antagonist) is now FDA-approved and effective for proptosis and diplopia
— Sight-threatening (optic neuropathy, corneal breakdown) → urgent IV steroids ± orbital decompression surgery
— Smoking cessation is the single most impactful modifiable factor
— Pretibial myxedema → high-potency topical steroids under occlusion
— Thionamide: agranulocytosis, hepatotoxicity, ANCA vasculitis
— RAI: transient hyperthyroid flare (1–2 weeks post), permanent hypothyroidism (expected), TED worsening
— Surgery: RLN injury (hoarseness), hypoparathyroidism (perioral numbness, Chvostek/Trousseau, tetany)
Key distinction: In storm, give PTU BEFORE iodine (~1 hour). Iodine first → substrate for new hormone synthesis = worsening. PTU/MMI blocks synthesis; then iodine blocks release via Wolff-Chaikoff.
— Thyroid storm (Burch-Wartofsky ≥45) — always ICU
— Hemodynamic instability, decompensated high-output CHF
— Severe arrhythmia not controlled with IV β-blockade
— Agranulocytosis with neutropenic sepsis
— Severe symptomatic hyperthyroidism with HR >130 not tolerating PO meds
— Thionamide-induced hepatotoxicity (ALT >3× ULN) requiring monitoring and treatment switch
— Active thionamide reaction with fever and oral ulcers pending CBC
— Preop optimization for urgent thyroidectomy
— Endocrinology: all newly diagnosed Graves; mandatory before RAI or surgery; co-management in pregnancy
— Ophthalmology: any TED symptoms; urgent same-day for vision loss, color desaturation, severe proptosis with exposure keratopathy
— Maternal-Fetal Medicine: pregnant patient with Graves, especially TRAb >3× ULN
— ENT/endocrine surgery: surgical candidates; preop vocal cord exam
— Cardiology: new AF, HF, or significant CAD interaction
— Hematology (or ID): agranulocytosis with sepsis
— Worsening AMS, fever >38.5°C, HR persistently >130 on β-blocker
— Inability to tolerate PO ATDs (vomiting from hyperthyroidism)
— Suspected adrenal insufficiency in setting of severe thyrotoxicosis
— Resolution of CNS dysfunction, T <38°C, HR <100, hemodynamics stable on PO meds, ATD/β-blocker tolerated, follow-up arranged within 1 week
— Closed-loop referral: confirm endo and ophtho appointments scheduled before discharge
— Provide written warning signs: fever + sore throat (agranulocytosis), jaundice (hepatotoxicity), vision change (TED progression)
CCS pearl: In thyroid storm CCS case, you must enter all five elements: PTU, iodine (delayed by 1h), propranolol, hydrocortisone, cooling/fluids — plus treat the trigger (often infection: cultures, empiric antibiotics).
— Older patients, long-standing nodular goiter, gradual onset, no orbitopathy, no TRAb
— RAIU: patchy/heterogeneous uptake with hot and cold areas
— Treatment: RAI (often higher dose) or thyroidectomy; ATDs not curative
— Single autonomous nodule; RAIU shows single hot nodule with suppression of surrounding tissue
— Treatment: RAI, surgery (lobectomy), or ethanol ablation
— Post-viral, painful tender goiter, elevated ESR/CRP, transient hyperthyroid phase → hypothyroid phase → recovery
— RAIU low (<5%); treat with NSAIDs, prednisone if severe; β-blocker for symptoms; no thionamide
— Autoimmune (TPO+), painless, low RAIU, self-limited; postpartum form within 12 months of delivery
— Treat symptomatically; many develop permanent hypothyroidism years later — monitor TSH annually
— Exogenous levothyroxine ingestion; low thyroglobulin (distinguishes from endogenous); low RAIU
— Common in healthcare workers, weight-loss attempts
— After contrast load, amiodarone, kelp; underlying nodular disease often present
— Type 1: iodine substrate effect on autonomous nodules → increased Doppler flow → thionamide ± perchlorate
— Type 2: destructive thyroiditis → decreased Doppler flow → glucocorticoids
— Rare; ectopic thyroid tissue; whole-body iodine scan localizes
— Hyperemesis gravidarum, hydatidiform mole, choriocarcinoma — transient, TRAb negative
— Inappropriately normal/high TSH with elevated FT4; pituitary MRI
Key distinction: RAIU + TRAb sort 90% of differentials: High RAIU + TRAb+ = Graves; High RAIU + TRAb– = nodular disease; Low RAIU = thyroiditis, exogenous, or iodine load.
— Pheochromocytoma: episodic HTN, headaches, palpitations, diaphoresis; plasma free metanephrines elevated; coexists with MEN2 — important not to miss when "hyperadrenergic" picture is the framing
— Generalized anxiety / panic disorder: normal TFTs, no weight loss, no proptosis, no goiter
— Substance use: cocaine, amphetamines, MDMA — tox screen
— Caffeine/energy drink overuse and stimulant medications (methylphenidate, decongestants)
— Withdrawal syndromes: alcohol, benzodiazepine, opioid withdrawal — adrenergic surge
— Malignancy (lymphoma, GI/lung): weight loss, fatigue, night sweats; B symptoms ≠ thyrotoxicosis
— Diabetes mellitus / DKA: weight loss, polyuria, tachycardia; check glucose
— Adrenal insufficiency (especially in storm overlap): hyperpigmentation, hyponatremia, hyperkalemia
— Carcinoid syndrome: flushing, diarrhea, palpitations; 5-HIAA elevated
— Mastocytosis: flushing, GI symptoms; tryptase elevated
— Chronic infection (TB, HIV): weight loss, sweats, tachycardia
— Orbital cellulitis: acute, painful, febrile, unilateral — emergency
— Orbital tumor, AV fistula (carotid-cavernous): pulsatile proptosis, bruit; CT/MR angiography
— IgG4-related orbital disease, sarcoidosis, granulomatosis with polyangiitis — biopsy if atypical
— Myasthenia gravis: ptosis and diplopia but no proptosis; can coexist with Graves in autoimmune clusters
— Sepsis-induced tachyarrhythmia, alcohol-induced AF (holiday heart), PE — always check TSH in new AF regardless of context
Board pearl: New AF + weight loss + fine tremor → check TSH first. New AF + episodic severe HTN + diaphoresis → check metanephrines. Both can coexist with autoimmunity, but the workup branch points off the dominant feature.
— Continue β-blocker until euthyroid (4–8 weeks); taper as HR/symptoms allow
— Resume MMI if needed 3–7 days post-RAI for symptom bridging
— Start levothyroxine 1.6 µg/kg/day when FT4 falls below normal (usually 6–12 weeks); titrate to TSH 0.5–2.5 mIU/L
— Recheck TSH every 6–8 weeks until stable, then every 6–12 months lifelong
— Levothyroxine started POD #1 at 1.6 µg/kg/day (adjust for age, cardiac status — start lower in elderly/CAD)
— Calcium carbonate 1–3 g/day with calcitriol 0.25–0.5 µg BID for first 1–2 weeks; taper based on PTH and calcium trends
— Voice rest, monitor for hematoma 24–48h
— Recheck TSH 6 weeks postop
— TSH at 1, 3, 6, 12 months post-discontinuation, then annually — relapse rate ~50% within 1st year; counsel patient on symptom recognition
— Recurrence → offer definitive therapy (RAI or surgery)
— Smoking cessation — single most impactful intervention for TED prevention/progression; document at every visit
— Bone health: DEXA at diagnosis and after treatment; calcium 1000–1200 mg/day, vitamin D 800–2000 IU/day; treat osteoporosis per guidelines
— AF: anticoagulation per CHA₂DS₂-VASc; revisit need after euthyroidism (some patients normalize)
— CV risk: lipids, BP, HbA1c — autoimmune cluster screening with TPO, anti-Tg, A1c, B12, celiac serologies, ACTH/cortisol if symptoms suggest
Step 3 management: Every Graves patient eventually becomes hypothyroid — frame the discussion at diagnosis: "We're trading a difficult-to-control hyperthyroid disease for a well-controlled hypothyroid condition treated with one pill a day." This sets realistic expectations and adherence.
— On thionamides: TFTs (FT4, FT3, TSH) every 4–6 weeks until euthyroid, then every 2–3 months. TRAb at 12–18 months to predict remission
— Post-RAI: TFTs every 4–6 weeks for 6 months, then every 3 months × 6 months, then annually once on stable levothyroxine
— Post-thyroidectomy: TSH at 6 weeks, 3 months, 6 months, then annually; calcium at 1 week, 1 month if hypocalcemia occurred
— Pregnancy: TFTs every 2–4 weeks initially, every 4–6 weeks once stable; TRAb at first visit, 18–22 weeks, 30–34 weeks
— Symptoms: HR, weight, sleep, GI, mood, menses
— Labs: TFTs, CBC and LFTs only if symptomatic (not routine for thionamides)
— Bone: DEXA at baseline if postmenopausal or other risk factors; repeat in 1–2 years
— Eye: CAS score and visual acuity at each visit if TED present; ophthalmology q3–6 months in active disease
— Smoking cessation — every visit, prescribe varenicline/NRT, refer to counseling
— Adverse effect recognition: fever + sore throat → stop drug + CBC same day; jaundice/dark urine → LFTs; rash → outpatient evaluation
— Medication adherence: missed doses lead to flare; do not abruptly stop
— Pregnancy planning: contraception during instability; preconception counseling
— Iodine awareness: avoid kelp, excess seaweed, iodine-containing supplements during treatment; notify clinician if contrast CT planned
— Mental health: anxiety/depression are part of disease; reassess after euthyroidism — refer if persistent
— Resistance training during recovery to rebuild muscle mass lost to thyrotoxic myopathy
— Cardiac rehab consideration if significant cardiomyopathy
— Coordinate endo + PCP shared care plan; clarify who orders TFTs and titrates levothyroxine post-definitive therapy
— Use patient portal for results review and dose adjustments to reduce no-shows
Board pearl: Post-definitive therapy, do not chase TSH with rapid levothyroxine adjustments — TSH lags FT4 by 6–8 weeks. Adjust based on both TSH and FT4, and wait 6 weeks between dose changes.
— RAI consent must explicitly cover: permanent hypothyroidism (likely), need for lifelong levothyroxine, transient hyperthyroid flare, possible TED worsening (especially in smokers), radiation precautions, contraception requirements (6 months women, 3–4 months men), and the alternative options. Provide written materials at patient's reading level
— Surgical consent: RLN injury (hoarseness — may be permanent), hypoparathyroidism, hematoma, infection, scar, hypothyroidism, anesthesia risk
— Shared decision-making is standard of care — document patient values (e.g., wants to avoid surgery, plans pregnancy in 8 months) and align modality choice
— A pregnant patient declining ATD due to teratogenicity fears: ethically obligated to provide accurate risk-benefit data — untreated hyperthyroidism risks include miscarriage, preeclampsia, IUGR, preterm birth, fetal loss, and maternal thyroid storm, far exceeding ATD risk
— If patient refuses, document discussion, offer thyroidectomy as alternative, involve MFM
— Confidentiality around contraception and pregnancy testing prior to RAI — assess maturity, involve parents per state law
— Agranulocytosis warning: written instructions for fever/sore throat are a documented safety practice; failure to counsel is a known liability pattern
— Driving safety: severe symptomatic hyperthyroidism with cognitive impairment or untreated storm → advise against driving until controlled
— Occupational radiation: post-RAI patients should not return to childcare/teaching jobs for 5–7 days
— Pregnancy test before RAI is non-negotiable — performing RAI in undiagnosed pregnancy causes fetal thyroid ablation after week 10; document negative β-hCG within 72h of dose
— Highest-risk window: post-discharge before first endo visit. Closed-loop referral with scheduled appointment and medication reconciliation reduces readmission. Verify that PCP knows who is titrating thyroid meds
— RAI requires home isolation capability; uninsured patients may not afford surgery — engage social work; community health workers improve follow-up adherence
Step 3 management: Before ordering RAI, document: (1) negative pregnancy test, (2) shared decision-making note, (3) TED screen, (4) radiation precaution counseling, (5) follow-up scheduled. Missing any of these is a board-test favorite "next best step" trap.
Board pearl: If a stem mentions "orange-peel plaques on the shins" + diffuse goiter + suppressed TSH → answer is Graves, even without explicit eye findings.
— 32 yo F, 3 months of weight loss, palpitations, diarrhea, fine tremor, diffuse non-tender goiter with bruit, mild proptosis. Next step? → TSH (suppressed), FT4 (elevated), TRAb (positive) — answer is Graves disease; start MMI + β-blocker
— Patient on MMI 10 mg/day with positive pregnancy test at 6 weeks. Next step? → Switch to PTU for 1st trimester, then transition back to MMI at 16 weeks
— Patient on MMI 3 weeks, now fever 39°C and sore throat, WBC 1.2 with ANC 200. Next step? → Stop MMI, do not start PTU (cross-reactivity), broad-spectrum antibiotics, supportive care; later definitive treatment with RAI or surgery
— Postop patient develops T 40°C, HR 160 AF, agitation, jaundice. Burch-Wartofsky 70. Order? → PTU first, then iodine 1 hour later, propranolol, hydrocortisone, cooling, treat trigger
— Painful tender goiter, ESR 80, suppressed TSH, RAIU <2%. → Subacute thyroiditis — NSAIDs/prednisone + β-blocker, not thionamide or RAI
— Graves patient with new decreased color vision and RAPD. Next step? → Emergent ophthalmology, IV methylprednisolone, consider orbital decompression — sight-threatening optic neuropathy
— 4 months postpartum, palpitations, weight loss, suppressed TSH. Next step? → Differentiate: TRAb+, high RAIU, goiter = postpartum Graves; TRAb–, low RAIU, painless = postpartum thyroiditis (β-blocker only)
— Graves patient + active moderate TED + smoker. Best treatment? → Thyroidectomy (or ATDs with later reconsideration); RAI relatively contraindicated; counsel smoking cessation
— 72 yo with TSH 0.05, normal FT4. Next step? → Repeat in 3 months; if persistent → treat (AF and fracture risk)
— Pregnant Graves patient at 22 weeks with TRAb 6× ULN. Next step? → MFM referral, serial fetal ultrasounds for goiter, growth, HR, hydrops
Step 3 management: Recognize "switch PTU→MMI at 2nd trimester" and "PTU before iodine in storm" — these directional/timing answers separate Step 3 takers.
Graves disease — diagnosed by suppressed TSH + elevated FT4/FT3 + positive TRAb (or diffuse high RAIU) — is managed with shared decision-making among methimazole (or PTU in the first trimester of pregnancy and in storm), radioactive iodine, or thyroidectomy, layered with β-blockers for symptoms, smoking cessation and ophthalmology referral for orbitopathy, and lifelong TSH monitoring as patients transition to expected post-treatment hypothyroidism on levothyroxine.
Board pearl: When in doubt on Step 3, default to: β-blocker + methimazole today, TRAb + β-hCG drawn, endocrinology and ophthalmology referrals placed, smoking cessation counseled, and follow-up TFTs in 4–6 weeks — this answer is right more often than not for newly diagnosed Graves disease in the ambulatory setting.