What are the ATA (American Thyroid Association) 2025 guidelines for managing thyroid conditions, including hypothyroidism, hyperthyroidism, and thyroid cancer?

ATA 2025 Guidelines for Managing Thyroid Conditions

The 2025 American Thyroid Association guidelines for differentiated thyroid cancer emphasize individualized care through the DATA framework (Diagnosis, risk/benefit Assessment, Treatment decisions, and response Assessment), with notable shifts toward de-escalation strategies including expanded use of active surveillance, lobectomy, and ablative procedures. 1, 2

Key Updates in the 2025 ATA Guidelines

Framework for Thyroid Cancer Management

The 2025 guidelines introduce a structured patient journey approach that differs significantly from the 2015 version:

• The DATA framework guides clinical decision-making from initial diagnosis through long-term surveillance, emphasizing shared decision-making between clinicians and patients 1, 2
• Molecular diagnostics now play an expanded role in risk stratification and treatment planning, moving beyond traditional histopathology alone 1
• Complete remission is introduced as a new concept for defining treatment success, representing a shift from previous terminology 1

Initial Treatment Decisions

For low-risk differentiated thyroid cancer, lobectomy is now more strongly endorsed as an alternative to total thyroidectomy, particularly for tumors ≤2 cm without extrathyroidal extension or lymph node metastases. 1, 2

• Active surveillance is explicitly included as a management option for very low-risk papillary thyroid cancers, particularly microcarcinomas ≤1 cm 1, 2
• Thermal ablation procedures (radiofrequency, microwave, laser) are recognized as treatment options for select patients who refuse surgery or have significant surgical contraindications 3

Radioactive Iodine (RAI) Therapy

The 2025 guidelines continue the trend toward selective RAI use established in 2015:

• RAI is not routinely recommended for low-risk patients following lobectomy or total thyroidectomy 3
• For intermediate-risk patients, RAI decisions should incorporate tumor features, patient factors, and institutional capabilities rather than following a uniform protocol 3
• When RAI is administered, low activities (30 mCi/1.1 GBq) following rhTSH are equivalent to high activities (100 mCi/3.7 GBq) following levothyroxine withdrawal for successful ablation 3

TSH Suppression Therapy

Target TSH levels are now more nuanced based on ongoing risk assessment rather than initial risk alone:

• For patients with excellent response to therapy (undetectable thyroglobulin, negative imaging), TSH targets of 0.5-2.0 mIU/L are appropriate 3
• For biochemical incomplete or indeterminate responses, mild suppression (TSH 0.1-0.5 mIU/L) may be indicated 3
• For structural incomplete responses, more aggressive suppression (TSH <0.1 mIU/L) remains appropriate 3
• Avoid chronic TSH suppression below 0.1 mIU/L in elderly patients or those with cardiac disease due to increased risks of atrial fibrillation and bone loss 4, 5

Surveillance and Monitoring

The 2025 guidelines emphasize de-escalation of surveillance for low-risk patients:

• For patients achieving complete remission, surveillance intervals can be extended beyond the traditional annual follow-up 1
• Ultrasound surveillance should be risk-adapted, with low-risk patients potentially requiring less frequent imaging 1, 2
• Thyroglobulin monitoring remains central, with stimulated thyroglobulin <1 ng/mL and suppressed thyroglobulin <0.2 ng/mL defining excellent response 3

Advanced Disease Management

• External beam radiation therapy and chemoradiotherapy are now included with more specific indications for locoregional disease not amenable to surgery or RAI 1
• For RAI-refractory disease with structural progression, systemic therapy with tyrosine kinase inhibitors should be considered when disease threatens critical structures or causes symptoms 1, 2

Hypothyroidism Management (Unchanged from Prior Guidelines)

For primary hypothyroidism, levothyroxine monotherapy remains the standard treatment, with dosing of approximately 1.6 mcg/kg/day for most adults. 4, 5, 6

Initiation and Dosing

• Start with 25-50 mcg/day in patients >70 years, those with cardiac disease, or multiple comorbidities to avoid precipitating cardiac complications 4, 5
• For younger patients without cardiac disease, full replacement doses can be initiated immediately 4
• Always rule out adrenal insufficiency before starting levothyroxine, as thyroid hormone can precipitate adrenal crisis in untreated adrenal insufficiency 4, 7

Monitoring

• Recheck TSH every 6-8 weeks during dose titration until target TSH (0.5-4.5 mIU/L) is achieved 4, 6
• Once stable, monitor TSH every 6-12 months or when symptoms change 4
• Approximately 25% of patients on levothyroxine are inadvertently overtreated with TSH suppression, increasing risks for atrial fibrillation, osteoporosis, and fractures 4

Treatment of Subclinical Hypothyroidism

• Treat with levothyroxine when TSH >10 mIU/L, regardless of symptoms, due to ~5% annual risk of progression to overt hypothyroidism 4, 6
• For TSH 4.5-10 mIU/L, treatment decisions should consider symptoms, positive anti-TPO antibodies, pregnancy planning, or goiter presence 4, 6
• Confirm elevated TSH with repeat testing after 3-6 weeks, as 30-60% of elevations normalize spontaneously 4

Hyperthyroidism Management (Based on 2011 Guidelines)

For Graves' disease, treatment options include radioactive iodine, antithyroid drugs (methimazole preferred over propylthiouracil except in first trimester pregnancy), or thyroidectomy, with choice based on patient factors and preferences. 8

Antithyroid Drug Selection

• Methimazole is preferred over propylthiouracil in non-pregnant adults due to lower risk of hepatotoxicity 7, 8
• Propylthiouracil may be preferred in first trimester pregnancy due to lower risk of fetal abnormalities, but consider switching to methimazole for second and third trimesters 7
• Monitor for hepatotoxicity with propylthiouracil, particularly in the first 6 months, with immediate discontinuation if liver dysfunction develops 7

Special Populations

• In pregnancy, maintain free T4 in upper third of normal range to avoid fetal hypothyroidism while treating maternal hyperthyroidism 8
• For pediatric patients, avoid propylthiouracil due to severe hepatotoxicity risk including hepatic failure requiring transplantation 7
• In elderly patients or those with cardiac disease, consider beta-blockade prior to definitive therapy to prevent cardiac complications 8

Critical Pitfalls to Avoid

• Never start levothyroxine before ruling out adrenal insufficiency in suspected central hypothyroidism, as this precipitates adrenal crisis 4, 7
• Avoid treating based on single elevated TSH value without confirmation, as 30-60% normalize on repeat testing 4
• Do not maintain chronic TSH suppression <0.1 mIU/L unless treating high-risk thyroid cancer with structural disease, due to cardiac and bone risks 3, 4
• For patients on propylthiouracil, immediately discontinue and check liver function if symptoms of hepatotoxicity develop (anorexia, jaundice, right upper quadrant pain) 7
• Avoid routine RAI administration in low-risk differentiated thyroid cancer patients, as surveillance is non-inferior for this population 3, 1