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endo.hyperthyroidism.core.v1PRODUCTION
endo.hyperthyroidism.core.v1

Hyperthyroidism / thyrotoxicosis (Graves / toxic nodule / thyroiditis — standalone core)

endocrinologychronicadultgeriatricpregnancy
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12/12 authored

Canonical 12-phase frame with authored status for this dossier.

Current phase

Frame

Detailed

Thyrotoxicosis is an AETIOLOGY question to be answered before definitive therapy: Graves vs toxic multinodular vs toxic adenoma vs thyroiditis (subacute/painless/post-partum/amiodarone-type-2/checkpoint) vs amiodarone-type-1 vs factitious vs iodine-induced vs TSH-oma. RAIU + TRAb + thyroglobulin + Doppler is the Bayesian discriminator set. Thyroid storm is screened and ROUTED OUT to endo.thyroid-storm.core.v1 (ATA 2016 Ross)

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Scope set to ambulatory thyrotoxicosis with the aetiology-discrimination frame explicit and storm excluded as the engine target

Patient inputs (18)

Elderly present with apathetic thyrotoxicosis (subtle — weight loss, AF, depression); subclinical treat-threshold lower at age ≥65; toxic nodular disease more common with age

Pregnancy contraindicates RAI, mandates PTU in 1st trimester then MMI, lowest effective dose, and TRAb for fetal/neonatal thyrotoxicosis risk

Recent iodinated contrast / amiodarone makes RAIU uninterpretable (conditional dependence) and causes Jod-Basedow iodine-induced thyrotoxicosis

Amiodarone type 1 (thionamide ± perchlorate) vs type 2 (glucocorticoid); checkpoint-inhibitor thyroiditis is transient → hypothyroid

AF / ischaemic heart disease raises urgency of control and lowers the subclinical treat-threshold; beta-blocker selection

EUGOGO activity/severity (mild vs moderate-severe vs sight-threatening) selects selenium vs IV glucocorticoid vs teprotumumab and contraindicates RAI in active/severe GO

Smoking strongly worsens Graves orbitopathy and reduces treatment response — cessation is a disease-modifying intervention

Primary screening analyte; suppressed/undetectable in primary thyrotoxicosis (non-suppressed with high FT4 flags TSH-oma / interference)

Distinguishes overt (high FT4 and/or FT3) from subclinical (normal FT4/FT3); T3-toxicosis pattern informs aetiology

TSH-receptor antibody is the Graves rule-in pivot — sens 97–98%, spec 97–99% (Tozzoli); guides ATD duration, pregnancy, remission prediction

Hyperthermia, altered mental status, CHF, GI dysfunction (Burch-Wartofsky) — screen for thyroid storm → escalate OUT to endo.thyroid-storm.core.v1

RAIU + scan is the master MECE pivot: diffuse↑ Graves / focal↑ toxic nodule / low = thyroiditis/factitious/iodine-induced (uninterpretable after iodine load or in pregnancy)

LOW/suppressed thyroglobulin is the decisive discriminator for factitious (exogenous-hormone) thyrotoxicosis vs all endogenous causes

Markedly elevated with a painful tender goitre identifies subacute (de Quervain) thyroiditis (low-RAIU, self-limited — no thionamide)

Doppler vascularity separates Graves / amiodarone type 1 (hypervascular) from amiodarone type 2 (destructive, absent flow → glucocorticoid-responsive); sizes nodules

Prior agranulocytosis / hepatotoxicity / vasculitis on a thionamide is an absolute contraindication to that drug class branch — drives definitive therapy

Febrile sore throat on a thionamide → STOP drug + urgent CBC with differential (agranulocytosis ~0.2–0.5%) before any further dose

Baseline + symptom-driven LFTs — PTU hepatotoxicity (can be fulminant) and methimazole cholestasis monitoring

* = hard-required. Engine cannot meaningfully run until these are filled.

Severity triggers (10)

10 need judgement
  • informationallife_threateningthyroid_storm_decompensation
    Hyperthermia + altered mental status + cardiac failure / GI-hepatic dysfunction in a thyrotoxic patient (Burch-Wartofsky high) — thyroid storm (ATA 2016 Ross)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningthionamide_agranulocytosis
    Fever + sore throat / mucosal ulceration on methimazole or PTU — agranulocytosis (~0.2–0.5%) (ATA 2016 Ross; ETA 2018 Kahaly)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningsight_threatening_graves_orbitopathy
    Dysthyroid optic neuropathy / corneal breakdown / rapidly progressive proptosis in Graves orbitopathy (EUGOGO 2021 Bartalena)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereptu_hepatotoxicity
    Jaundice / RUQ pain / transaminase surge on propylthiouracil (can be fulminant) or methimazole cholestasis (ATA 2017 Alexander)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverepregnancy_or_preconception_thyrotoxic
    Pregnant or pre-conception woman with Graves/overt thyrotoxicosis, or elevated TRAb in pregnancy (ATA 2017 Alexander)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereamiodarone_induced_thyrotoxicosis_agranulocytosis_amplified
    Thyrotoxicosis on/after amiodarone (AIT) requiring a thionamide — ATD-agranulocytosis risk is ~6× the background thyrotoxicosis risk (conditional-on-drug dependency) (Gershinsky Thyroid 2019)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderategeriatric_apathetic_thyrotoxicosis_with_af
    Older patient with apathetic thyrotoxicosis presenting as new atrial fibrillation / weight loss / depression rather than classic adrenergic features (ATA 2016 Ross)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatesubclinical_hyperthyroidism_high_risk
    Persistently suppressed TSH <0.1 mIU/L with normal FT4/FT3 AND a risk modifier (age ≥65 / AF / cardiac disease / osteoporosis) — CONDITIONAL treat-threshold (modifier presence lowers the TSH at which treatment is indicated) (ATA 2016 Ross)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmildthyrotoxic_menstrual_dysfunction_aub_o
    Reproductive-age woman with thyrotoxicosis and oligomenorrhoea / amenorrhoea / abnormal uterine bleeding — endocrine (AUB-O) contributor; thyroid is also a Rotterdam-PCOS exclusion (ATA 2016 Ross)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmildantithyroid_over_treatment_iatrogenic_hypothyroid
    Rising TSH ± low FT4 on a thionamide — iatrogenic hypothyroidism from over-treatment (ATA 2016 Ross)
    Trigger could not be auto-evaluated — needs clinician judgement.

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Recommended regimen

Thyrotoxicosis aetiology gate → beta-blocker → methimazole first-line → definitive (RAI vs surgery) → Graves-orbitopathy ladder → pregnancy → amiodarone-induced (ATA 2016 Ross; ETA 2018 Kahaly; ATA 2017 Alexander; EUGOGO 2021 Bartalena)
axis: hyperthyroidism_aetiology_then_definitive_ladderstep 1 - Step 1 — Aetiology gate: destructive thyroiditis & factitious get NO thionamide
Selected step "Step 1 — Aetiology gate: destructive thyroiditis & factitious get NO thionamide" — Any thyrotoxic patient before committing to antithyroid drug
  • radioiodine uptake & scan + TRAb + thyroglobulin + thyroid Doppler
    first line
    aetiology_discrimination
    triggers: suppressed_tsh_high_ft4_ft3, trab_negative_or_equivocal
    ATA 2016 Ross — master MECE pivot: diffuse↑RAIU=Graves, focal↑=toxic nodular, LOW=thyroiditis/factitious/iodine-induced; low thyroglobulin=factitious; Doppler separates amiodarone type 1 vs 2 (Tanda 2008)
  • supportive only — no thionamide (destructive thyroiditis / factitious / iodine-induced low-RAIU)
    first line
    treatment_deferral
    triggers: subacute_thyroiditis, painless_or_postpartum_thyroiditis, amiodarone_type_2, checkpoint_inhibitor_thyroiditis, factitious_low_thyroglobulin
    ATA 2016 Ross — destructive/exogenous thyrotoxicosis is self-limited; thionamide is ineffective and harmful; treat symptoms only and retest (hypothyroid phase expected in thyroiditis)
  • NSAID then short oral glucocorticoid taper for painful subacute thyroiditis
    comorbidity specific
    anti_inflammatory
    triggers: subacute_de_quervain_thyroiditis_pain
    ATA 2016 Ross — NSAID first for pain; prednisone taper if severe/unresponsive pain; NOT a thionamide indication

outpatient playbook — drug actions (7)

  1. 1. aetiology gate — supportive only if destructive thyroiditis/factitious; no thionamide
    no antithyroid drug • n/a • once
    trigger: Low-RAIU / low-thyroglobulin / painful subacute
    Destructive/exogenous thyrotoxicosis is self-limited — thionamide ineffective/harmful (ATA 2016 Ross)
  2. 2. propranolol (or atenolol)
    propranolol 10–40 mg q6–8h titrate • PO • q6–8h
    trigger: Symptomatic thyrotoxicosis any aetiology
    Adrenergic symptom relief; high-dose propranolol also blunts T4→T3 (ATA 2016 Ross)
  3. 3. methimazole first-line (PTU only 1st-tri/storm)
    10–30 mg/day → 5–10 mg/day maintenance titrated to FT4 • PO • once daily
    trigger: Graves or toxic nodular, not 1st-tri pregnant
    ATA 2016 Ross / ETA 2018 Kahaly — once-daily, less hepatotoxic than PTU; 12–18 mo Graves course
  4. 4. definitive — RAI or thyroidectomy
    RAI fixed/dosimetry single dose; or total thyroidectomy (high-volume) • PO / surgical • single
    trigger: ATD relapse/intolerance, toxic nodular, large goitre, patient choice
    ATA 2016 Ross — RAI contraindicated in pregnancy/severe-active-GO/lactation; surgery render euthyroid + iodide pre-op for Graves
  5. 5. Graves orbitopathy ladder
    selenium 100 µg BID (mild) → IV methylprednisolone 4.5 g/12 wk (mod-severe) → teprotumumab 10→20 mg/kg q3wk ×8 • PO/IV • per tier
    trigger: Graves orbitopathy by EUGOGO tier
    EUGOGO 2021 Bartalena; OPTIC Douglas 2020 (proptosis 83% vs 10%, NNT 1.36)
  6. 6. pregnancy ATD
    PTU lowest dose 1st-tri → MMI 2nd/3rd-tri; TRAb surveillance • PO • BID-TID/daily
    trigger: Pregnant/pre-conception Graves
    ATA 2017 Alexander — avoid MMI embryopathy 1st-tri; TRAb → fetal/neonatal risk
  7. 7. amiodarone-induced type-specific
    type 1 methimazole 20–40 mg ± perchlorate; type 2 prednisone 0.5–0.7 mg/kg • PO • daily
    trigger: AIT type by Doppler
    Tanda 2008 — type 1 thionamide, type 2 glucocorticoid; mixed get both

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Suppressed/undetectable TSH on screening or opportunistic testing (ATA 2016 Ross); Heat intolerance / weight loss / palpitations / tremor / anxiety / oligomenorrhoea (ATA 2016 Ross); New atrial fibrillation / unexplained sinus tachycardia → screen thyroid (ATA 2016 Ross).

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**Hyperthyroidism / thyrotoxicosis (Graves / toxic nodule / thyroiditis — standalone core)** (endo.hyperthyroidism.core.v1).
Phenotype framing: MECE terminal aetiology: Graves (TRAb+, diffuse↑RAIU, orbitopathy) vs toxic multinodular goitre (patchy↑RAIU) vs toxic adenoma (focal↑RAIU) vs thyroiditis — subacute de Quervain (painful, ↑ESR, low RAIU) / painless / post-partum / amiodarone type 2 / checkpoint-inhibitor — vs amiodarone type 1 (iodine-induced) vs factitious (LOW thyroglobulin) vs iodine-induced Jod-Basedow vs TSH-secreting adenoma (non-suppressed TSH). RAIU is the master split; TRAb / tenderness+ESR / thyroglobulin / Doppler are the named pivots (ATA 2016 Ross)
Scope: Thyrotoxicosis is an AETIOLOGY question to be answered before definitive therapy: Graves vs toxic multinodular vs toxic adenoma vs thyroiditis (subacute/painless/post-partum/amiodarone-type-2/checkpoint) vs amiodarone-type-1 vs factitious vs iodine-induced vs TSH-oma. RAIU + TRAb + thyroglobulin + Doppler is the Bayesian discriminator set. Thyroid storm is screened and ROUTED OUT to endo.thyroid-storm.core.v1 (ATA 2016 Ross)

No severity triggers fired against current inputs.

Plan

Regimen axis: **Thyrotoxicosis aetiology gate → beta-blocker → methimazole first-line → definitive (RAI vs surgery) → Graves-orbitopathy ladder → pregnancy → amiodarone-induced (ATA 2016 Ross; ETA 2018 Kahaly; ATA 2017 Alexander; EUGOGO 2021 Bartalena)** — step "Step 1 — Aetiology gate: destructive thyroiditis & factitious get NO thionamide".
1. radioiodine uptake & scan + TRAb + thyroglobulin + thyroid Doppler (aetiology_discrimination, first line) — ATA 2016 Ross — master MECE pivot: diffuse↑RAIU=Graves, focal↑=toxic nodular, LOW=thyroiditis/factitious/iodine-induced; low thyroglobulin=factitious; Doppler separates amiodarone type 1 vs 2 (Tanda 2008)
2. supportive only — no thionamide (destructive thyroiditis / factitious / iodine-induced low-RAIU) (treatment_deferral, first line) — ATA 2016 Ross — destructive/exogenous thyrotoxicosis is self-limited; thionamide is ineffective and harmful; treat symptoms only and retest (hypothyroid phase expected in thyroiditis)
3. NSAID then short oral glucocorticoid taper for painful subacute thyroiditis (anti_inflammatory, comorbidity specific) — ATA 2016 Ross — NSAID first for pain; prednisone taper if severe/unresponsive pain; NOT a thionamide indication

Setting playbook (outpatient) — Discriminate the thyrotoxicosis aetiology (RAIU + TRAb + Tg + Doppler), control symptoms with a beta-blocker, treat Graves/toxic-nodular with methimazole first-line then definitive therapy, manage orbitopathy/pregnancy/geriatric/amiodarone special cases, avoid over-treatment, and route storm out (ATA 2016 Ross; ETA 2018 Kahaly; ATA 2017 Alexander; EUGOGO 2021 Bartalena)
4. aetiology gate — supportive only if destructive thyroiditis/factitious; no thionamide no antithyroid drug n/a once — Low-RAIU / low-thyroglobulin / painful subacute (Destructive/exogenous thyrotoxicosis is self-limited — thionamide ineffective/harmful (ATA 2016 Ross))
5. propranolol (or atenolol) propranolol 10–40 mg q6–8h titrate PO q6–8h — Symptomatic thyrotoxicosis any aetiology (Adrenergic symptom relief; high-dose propranolol also blunts T4→T3 (ATA 2016 Ross))
6. methimazole first-line (PTU only 1st-tri/storm) 10–30 mg/day → 5–10 mg/day maintenance titrated to FT4 PO once daily — Graves or toxic nodular, not 1st-tri pregnant (ATA 2016 Ross / ETA 2018 Kahaly — once-daily, less hepatotoxic than PTU; 12–18 mo Graves course)
7. definitive — RAI or thyroidectomy RAI fixed/dosimetry single dose; or total thyroidectomy (high-volume) PO / surgical single — ATD relapse/intolerance, toxic nodular, large goitre, patient choice (ATA 2016 Ross — RAI contraindicated in pregnancy/severe-active-GO/lactation; surgery render euthyroid + iodide pre-op for Graves)
8. Graves orbitopathy ladder selenium 100 µg BID (mild) → IV methylprednisolone 4.5 g/12 wk (mod-severe) → teprotumumab 10→20 mg/kg q3wk ×8 PO/IV per tier — Graves orbitopathy by EUGOGO tier (EUGOGO 2021 Bartalena; OPTIC Douglas 2020 (proptosis 83% vs 10%, NNT 1.36))
9. pregnancy ATD PTU lowest dose 1st-tri → MMI 2nd/3rd-tri; TRAb surveillance PO BID-TID/daily — Pregnant/pre-conception Graves (ATA 2017 Alexander — avoid MMI embryopathy 1st-tri; TRAb → fetal/neonatal risk)
10. amiodarone-induced type-specific type 1 methimazole 20–40 mg ± perchlorate; type 2 prednisone 0.5–0.7 mg/kg PO daily — AIT type by Doppler (Tanda 2008 — type 1 thionamide, type 2 glucocorticoid; mixed get both)

Non-pharmacologic actions:
- Radioiodine uptake & scan + thyroid ultrasound/Doppler for aetiology (ATA 2016 Ross)
- Smoking cessation — disease-modifying for Graves orbitopathy (EUGOGO 2021 Bartalena)
- Referral to high-volume thyroid surgeon if surgical candidate (ATA 2016 Ross)
- Pre-conception counselling — switch-to-PTU plan or definitive therapy before pregnancy (ATA 2017 Alexander)
- Route post-ablation hypothyroidism to endo.hypothyroidism.core.v1; dominant nodule to workup.thyroid_nodule (ATA 2016 Ross)

AVOID / contraindication checks:
- Radioiodine_contraindicated_in_pregnancy_lactation_and_severe_active_orbitopathy (ATA 2016 Ross 27521067; EUGOGO 2021 Bartalena 34297684)
- Methimazole_contraindicated_in_first_trimester_pregnancy_use_PTU_then_switch_back_after_first_trimester (ATA 2017 Alexander 28056690)
- Thionamide_agranulocytosis_~0.2_to_0.5pct_febrile_sore_throat_STOP_drug_and_urgent_CBC (ATA 2016 Ross 27521067; ETA 2018 Kahaly 30283735)
- PTU_hepatotoxicity_can_be_fulminant_>_methimazole_reserve_PTU_for_first_trimester_and_storm (ATA 2017 Alexander 28056690)
- RAI_can_worsen_active_Graves_orbitopathy_use_steroid_prophylaxis_if_mild_active_GO_or_choose_ATD_surgery (Bartalena NEJM 1998 9420337; EUGOGO 2021 34297684)
- Do_not_give_thionamide_for_destructive_thyroiditis_or_factitious_thyrotoxicosis_supportive_only (ATA 2016 Ross 27521067)
- Potassium_iodide_pre_thyroidectomy_only_NOT_before_RAI_blocks_uptake (ATA 2016 Ross 27521067)
- Thyroid_storm_decompensation_escalate_to_endo.thyroid storm.core.v1 (acute engine; not managed here)
- RAI_modest_long_term_solid_cancer_mortality_dose_signal_counsel (Kitahara JAMA Intern Med 2019 31260066)
- Amiodarone_type_2_glucocorticoid_responsive_not_thionamide_distinguish_by_Doppler (Tanda 2008 18410546)

Monitoring

Regimen monitoring:
- FT4/FT3 every 4–6 weeks on thionamide until euthyroid then every 2–3 months (TSH lags — do not titrate to TSH early) (ATA 2016 Ross 27521067)
- baseline + symptom-driven CBC with differential (agranulocytosis ~0.2–0.5%) — counsel febrile-sore-throat STOP rule (ATA 2016 Ross 27521067)
- baseline + symptom-driven LFTs (PTU fulminant hepatotoxicity; MMI cholestasis) (ATA 2017 Alexander 28056690)
- TRAb at 12–18 months predicts Graves remission vs relapse (Azizi Endocrine 2024 38165576)
- post-RAI / post-thyroidectomy TSH+FT4 surveillance for the near-universal hypothyroid endpoint → route to endo.hypothyroidism.core.v1 (ATA 2016 Ross 27521067)
- TRAb in pregnancy at initial visit and 18–22 wk if elevated/on ATD/prior ablation — fetal/neonatal thyrotoxicosis (ATA 2017 Alexander 28056690)
- orbitopathy activity/severity (EUGOGO) re-assessed at each visit; smoking-cessation reinforced (EUGOGO 2021 Bartalena 34297684)

Setting (outpatient) monitoring:
- FT4/FT3 q4–6 wk on thionamide until euthyroid then q2–3 mo (ATA 2016 Ross)
- Baseline + symptom-driven CBC (agranulocytosis) and LFTs (hepatotoxicity); febrile-sore-throat STOP rule counselled (ATA 2016 Ross)
- TRAb at 12–18 mo (remission prediction) and in pregnancy (fetal risk) (ETA 2018 Kahaly; ATA 2017 Alexander)
- Post-RAI/post-op TSH+FT4 for the hypothyroid endpoint (ATA 2016 Ross)

Follow-up plan: Graves: assess remission after 12–18 mo MMI (TRAb-guided) — relapse → definitive therapy or long-term low-dose MMI (Azizi: long-term recurrence 17% vs conventional 56%; juvenile 4-yr cure 88% vs 33%). Lifelong levothyroxine after RAI/thyroidectomy (route to endo.hypothyroidism.core.v1). Pregnancy: TRAb in pregnancy → fetal/neonatal thyrotoxicosis surveillance; pre-conception counselling (switch to PTU plan / consider definitive before pregnancy). RAI long-term modest solid-cancer-mortality counselling (Kitahara). Return precautions: fever/sore throat, jaundice, eye pain/vision change, palpitations, pregnancy (ATA 2016 Ross; ETA 2018 Kahaly; ATA 2017 Alexander)
- Close-out criterion: Remission/definitive-therapy decision, lifelong-LT4 plan, pregnancy-TRAb surveillance and return precautions booked

Monitoring phase: On thionamide: TFTs (FT4/FT3 — TSH lags) every 4–6 weeks until euthyroid then every 2–3 months; baseline + symptom-driven CBC (agranulocytosis) and LFTs (hepatotoxicity); counsel febrile-sore-throat STOP rule. TRAb at 12–18 months predicts Graves remission vs relapse (Azizi). Post-RAI / post-thyroidectomy: surveil for the near-universal hypothyroid endpoint → route to endo.hypothyroidism.core.v1. Subacute thyroiditis: expect hypothyroid phase then recovery — serial TFTs. Watch over-treatment (iatrogenic hypothyroidism) (ATA 2016 Ross; ETA 2018 Kahaly)

Disposition

Current setting: outpatient — Discriminate the thyrotoxicosis aetiology (RAIU + TRAb + Tg + Doppler), control symptoms with a beta-blocker, treat Graves/toxic-nodular with methimazole first-line then definitive therapy, manage orbitopathy/pregnancy/geriatric/amiodarone special cases, avoid over-treatment, and route storm out (ATA 2016 Ross; ETA 2018 Kahaly; ATA 2017 Alexander; EUGOGO 2021 Bartalena)

Disposition criteria:
- Continue outpatient endocrinology once aetiology assigned and on an appropriate plan (ATA 2016 Ross)
- Escalate storm/decompensation to the acute engine; route post-ablation hypothyroid to endo.hypothyroidism.core.v1 (ATA 2016 Ross)

Escalation triggers (move to higher acuity):
- Hyperthermia + altered mental status + CHF/GI dysfunction (Burch-Wartofsky high) → ED, escalate to endo.thyroid-storm.core.v1 (ATA 2016 Ross)
- Febrile sore throat on thionamide → STOP drug, urgent CBC, treat as agranulocytosis until excluded (ATA 2016 Ross)
- Jaundice / RUQ pain / transaminase surge on PTU → stop, urgent hepatology (ATA 2017 Alexander)
- Sight-threatening orbitopathy (vision loss / dysthyroid optic neuropathy / corneal breakdown) → urgent IV methylprednisolone + oculoplastics (EUGOGO 2021 Bartalena)

Patient Action Plan

**Hyperthyroidism / antithyroid-drug self-management plan**
Personalised values: aetiology, antithyroid_drug_and_dose, beta_blocker, definitive_therapy_plan, pregnancy_plan, orbitopathy_status.

**Stable, symptoms controlled, no danger signs** (green):
Triggers:
- Heart rate, tremor and weight stable on your current treatment (ATA 2016 Ross)
- No fever, sore throat, jaundice or eye changes
- Taking your antithyroid medicine exactly as prescribed
Actions:
- Take methimazole (or your prescribed antithyroid drug) every day as directed (ATA 2016 Ross)
- Keep your blood-test appointments (thyroid levels every 4–6 weeks until stable) (ATA 2016 Ross)
- Do not smoke — smoking worsens thyroid eye disease (EUGOGO 2021 Bartalena)
- If you are planning a pregnancy, contact your provider FIRST — the medicine plan changes (ATA 2017 Alexander)

**Warning — contact your provider promptly** (yellow):
Triggers:
- New or worsening eye bulging, double vision or eye pain (EUGOGO 2021 Bartalena)
- Symptoms returning (palpitations, tremor, weight loss) or becoming sluggish/cold (over-treatment)
- A positive pregnancy test while on an antithyroid drug
- Mild rash or joint aches after starting the drug
Actions:
- If newly pregnant on an antithyroid drug, contact your provider NOW — the drug usually needs changing (ATA 2017 Alexander)
- Do not change your own dose; arrange a thyroid blood test (ATA 2016 Ross)
- Report new eye symptoms the same week — early thyroid eye disease is treatable (EUGOGO 2021 Bartalena)
Contact provider when:
- Newly pregnant on an antithyroid drug (same day) (ATA 2017 Alexander)
- New or worsening eye bulging / double vision (EUGOGO 2021 Bartalena)
- Symptoms of too much OR too little thyroid hormone (ATA 2016 Ross)

**Emergency — stop the drug / seek urgent care** (red):
Triggers:
- Fever with a sore throat or mouth ulcers (possible agranulocytosis) (ATA 2016 Ross)
- Yellow skin/eyes, dark urine or severe upper-abdominal pain (liver injury) (ATA 2017 Alexander)
- High fever + confusion + racing heart + vomiting (possible thyroid storm) (ATA 2016 Ross)
- Sudden vision loss or severe eye pain (EUGOGO 2021 Bartalena)
Actions:
- STOP the antithyroid drug and get an urgent blood count for fever + sore throat (ATA 2016 Ross)
- Go to the emergency department now for confusion + high fever + racing heart — this can be thyroid storm (ATA 2016 Ross)
- Seek emergency eye care for sudden vision loss (EUGOGO 2021 Bartalena)
- Bring your medication list including your antithyroid drug and dose
Contact provider when:
- Always seek emergency care for fever + sore throat on a thionamide, jaundice, thyroid-storm features, or sudden vision loss (ATA 2016 Ross; ATA 2017 Alexander; EUGOGO 2021 Bartalena)

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] Hyperthermia + altered mental status + cardiac failure / GI-hepatic dysfunction in a thyrotoxic patient (Burch-Wartofsky high) — thyroid storm (ATA 2016 Ross)
- [LIFE_THREATENING] Fever + sore throat / mucosal ulceration on methimazole or PTU — agranulocytosis (~0.2–0.5%) (ATA 2016 Ross; ETA 2018 Kahaly)
- [LIFE_THREATENING] Dysthyroid optic neuropathy / corneal breakdown / rapidly progressive proptosis in Graves orbitopathy (EUGOGO 2021 Bartalena)

Citations

- ATA 2016 Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (Ross, Thyroid 2016) + ETA 2018 Graves Hyperthyroidism (Kahaly, Eur Thyroid J) + ATA 2017 Thyroid Disease in Pregnancy (Alexander) + EUGOGO 2021 Graves Orbitopathy (Bartalena, EJE); reconciled with OPTIC (Douglas NEJM 2020), the 2025 EUGOGO-vs-ATA/ETA-2022 comparison, long-term-ATD recurrence RCTs, the Danish nationwide ATD-embryopathy cohort (Andersen JCEM 2013), the AIT-amplified ATD-agranulocytosis cohort (Gershinsky Thyroid 2019), and the Thyroid Studies Collaboration fT4-AF IPD (Baumgartner Circulation 2017) [PMID:27521067](https://pubmed.ncbi.nlm.nih.gov/27521067/)
- Cited evidence (PMID 30283735) [PMID:30283735](https://pubmed.ncbi.nlm.nih.gov/30283735/)
- Cited evidence (PMID 28056690) [PMID:28056690](https://pubmed.ncbi.nlm.nih.gov/28056690/)
- Cited evidence (PMID 34297684) [PMID:34297684](https://pubmed.ncbi.nlm.nih.gov/34297684/)
- Cited evidence (PMID 41283777) [PMID:41283777](https://pubmed.ncbi.nlm.nih.gov/41283777/)

Last reconciled with current guidelines: 2026-05-17.
References
  • ATA 2016 Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (Ross, Thyroid 2016) + ETA 2018 Graves Hyperthyroidism (Kahaly, Eur Thyroid J) + ATA 2017 Thyroid Disease in Pregnancy (Alexander) + EUGOGO 2021 Graves Orbitopathy (Bartalena, EJE); reconciled with OPTIC (Douglas NEJM 2020), the 2025 EUGOGO-vs-ATA/ETA-2022 comparison, long-term-ATD recurrence RCTs, the Danish nationwide ATD-embryopathy cohort (Andersen JCEM 2013), the AIT-amplified ATD-agranulocytosis cohort (Gershinsky Thyroid 2019), and the Thyroid Studies Collaboration fT4-AF IPD (Baumgartner Circulation 2017) — PMID:27521067
  • Cited evidence (PMID 30283735) — PMID:30283735
  • Cited evidence (PMID 28056690) — PMID:28056690
  • Cited evidence (PMID 34297684) — PMID:34297684
  • Cited evidence (PMID 41283777) — PMID:41283777