Summary

The 2016 ATA guideline updates the diagnosis and management of hyperthyroidism and thyrotoxicosis, providing 124 evidence-based recommendations covering Graves’ disease (GD), toxic multinodular goiter (TMNG), toxic adenoma (TA), subclinical hyperthyroidism, pregnancy, pediatric disease, Graves’ orbitopathy (GO), thyroid storm, and amiodarone/iodine-induced thyrotoxicosis. Major changes from 2011 include new paradigms for etiology evaluation (TRAb as cost-effective first-line testing), revised antithyroid drug (ATD) management (methimazole preferred except first-trimester pregnancy), updated pregnancy guidance (switch MMI to PTU before/early in pregnancy, then consider switch back after first trimester), and expanded perioperative preparation guidance.

Key Recommendations

Determine etiology of thyrotoxicosis with TRAb measurement, radioactive iodine uptake (RAIU), or thyroidal Doppler; obtain 123I or 99mTc scan when TA or TMNG is suspected.
Use beta-adrenergic blockade in all symptomatic thyrotoxic patients, especially elderly or those with HR >90 bpm or cardiovascular disease.
Treat overt Graves’ hyperthyroidism with one of three modalities: radioactive iodine (RAI), ATDs, or thyroidectomy — chosen by patient preference and clinical context.
Use methimazole (MMI) as the ATD of choice in virtually all patients except first-trimester pregnancy (use PTU), thyroid storm, or MMI intolerance.
Continue MMI for 12–18 months for GD; check TRAb before stopping — persistently elevated TRAb predicts relapse and warrants definitive therapy or continued low-dose MMI.
Render patients euthyroid with MMI plus preoperative potassium iodide before thyroidectomy for GD; perform near-total/total thyroidectomy by a high-volume surgeon (>25 thyroidectomies/year).
For thyroid storm, use multimodal therapy: PTU (preferred over MMI for blocking T4→T3), beta-blocker, iodine (≥1 hour after ATD), hydrocortisone, cooling, and supportive ICU care.
For TMNG/TA, prefer RAI or surgery; ATDs do not induce remission and are reserved for elderly/poor surgical candidates.
In pregnancy, use PTU in first trimester; consider switching to MMI in second trimester; target maternal free T4 at or slightly above the upper limit of pregnancy reference range using lowest effective dose.
Measure TRAb in pregnant women with current/prior GD at initial visit and at 18–22 weeks (and 30–34 weeks if elevated) to assess fetal/neonatal hyperthyroidism risk.
Treat subclinical hyperthyroidism when TSH persistently <0.1 mU/L in those ≥65 years, postmenopausal women not on estrogen/bisphosphonate, patients with cardiac disease, osteoporosis, or hyperthyroid symptoms.
Avoid RAI in patients with moderate-to-severe or sight-threatening active Graves’ orbitopathy; use prophylactic glucocorticoids when RAI is given in mild active GO with risk factors (smoking, high TRAb).

Thresholds & Doses

Overt hyperthyroidism: TSH usually <0.01 mU/L (3rd-gen assay) with elevated free T4 and/or T3.
Subclinical hyperthyroidism treatment thresholds: TSH persistently <0.1 mU/L (treat per risk factors); TSH 0.1–0.4 mU/L (consider treatment in ≥65 years or high-risk).
Initial MMI dose by free T4: 5–10 mg/d if free T4 1–1.5× ULN; 10–20 mg/d if 1.5–2× ULN; 30–40 mg/d if 2–3× ULN.
PTU starting dose: 50–150 mg three times daily; maintenance 50 mg 2–3 times daily.
Discontinue PTU if transaminases >3× ULN (adults) or 2–3× ULN (children).
Baseline ATD contraindication thresholds: ANC <1000/mm³ or LFTs >5× ULN.
RAI for GD: typical dose 10–15 mCi (370–555 MBq); calculated dose >150 μCi/g (5.55 MBq/g) of thyroid tissue to achieve hypothyroidism.
RAI for TMNG: 150–200 μCi/g (5.55–7.4 MBq/g) corrected for 24-hour RAIU.
RAI for TA: fixed 10–20 mCi (370–740 MBq) or 150–200 μCi/g.
Hold MMI 2–3 days before RAI; resume 3–7 days after RAI in high-risk patients.
Pregnancy delay after RAI: ≥6 months for women; 3–4 months for men.
Preoperative iodine: Lugol’s 5–7 drops or SSKI 1–2 drops three times daily for 10 days before surgery.
Postoperative levothyroxine dose: 1.6 μg/kg/day (0.8 μg/lb); check TSH 6–8 weeks postop.
Postop calcium target ≥8.0 mg/dL (2.0 mmol/L); calcium carbonate 1250–2500 mg QID, calcitriol 0.5 μg daily.
Thyroid storm BWPS: ≥45 = thyroid storm; 25–44 = impending; <25 = unlikely.
Thyroid storm drug doses: PTU 500–1000 mg load then 250 mg q4h; MMI 60–80 mg/d; propranolol 60–80 mg q4h; SSKI 5 drops q6h (start ≥1 hr after ATD); hydrocortisone 300 mg IV load then 100 mg q8h.
Pediatric MMI dosing: infants 1.25 mg/d; ages 1–5 yr 2.5–5 mg/d; 5–10 yr 5–10 mg/d; 10–18 yr 10–20 mg/d.
Pediatric RAI: avoid in children <5 years; ages 5–10 acceptable if calculated dose <10 mCi (<370 MBq); use >150 μCi/g.
Pediatric pretreatment threshold: pretreat with MMI if total T4 >20 μg/dL or free T4 >5 ng/dL before RAI.
Pregnancy thyroid function reference: T4/T3 ranges increase to 1.5× nonpregnant ranges by 2nd/3rd trimester.
GO prophylactic prednisone with RAI: 0.4–0.5 mg/kg/day starting 1–3 days after RAI, tapered over 3 months (lower doses 0.2 mg/kg × 6 weeks may suffice).
Pediatric MMI duration: trial 1–2 years; remission rates 20–30% at 2 years.
Agranulocytosis incidence with ATDs: 0.1–0.3%, mostly within first 90 days.
Tylenol-style monitoring: thyroid function tests at 2–6 weeks after MMI initiation, then every 4–6 weeks until stable, then every 2–3 months.

Citations

Recommendation 1 (Section B3) — etiology determination using TRAb, RAIU, or Doppler
Recommendation 3, Table 5 — three treatment modalities for Graves’ hyperthyroidism
Recommendations 8–10 (Section D2) — RAI dosing 10–15 mCi and radiation safety for GD
Recommendation 13 (Section E1) — MMI as preferred ATD except first trimester pregnancy
Recommendations 22–23 (Section E8) — 12–18 month MMI course and TRAb-guided discontinuation
Recommendations 27–28 (Section F2) — near-total/total thyroidectomy by high-volume surgeon
Recommendations 34–35, Tables 6–7 — thyroid storm diagnosis (BWPS) and multimodality treatment
Recommendations 78–95, Table 11 — diagnosis and management of hyperthyroidism in pregnancy
Recommendations 73–76, Table 10 — subclinical hyperthyroidism treatment thresholds
Recommendations 99–108, Tables 12–14 — Graves’ orbitopathy assessment and treatment selection
Recommendations 111–116, Figure 1 — amiodarone-induced thyrotoxicosis evaluation and management
Recommendations 58–72 (Sections O–R) — pediatric Graves’ disease management