How to initiate levothyroxine (Synthroid) therapy in a patient?

How to Initiate Levothyroxine (Synthroid) Therapy

For patients under 70 years without cardiac disease, start levothyroxine at the full replacement dose of 1.6 mcg/kg/day (typically 75-100 mcg for women, 100-150 mcg for men); for patients over 70 years or with cardiac disease, start at 25-50 mcg/day and titrate gradually. 1, 2

Pre-Treatment Assessment

Before initiating levothyroxine, complete these critical steps:

• Rule out adrenal insufficiency first - Starting thyroid hormone before corticosteroids can precipitate life-threatening adrenal crisis, particularly in patients with suspected central hypothyroidism or hypophysitis 1, 3
• Confirm the diagnosis with repeat TSH testing after 3-6 weeks, as 30-60% of elevated TSH levels normalize spontaneously 1
• Measure both TSH and free T4 to distinguish subclinical hypothyroidism (normal free T4) from overt hypothyroidism (low free T4) 1
• Screen for cardiac disease including coronary artery disease and atrial fibrillation, as these require modified dosing 1, 3

Initial Dosing Algorithm

For Younger Patients Without Cardiac Disease (<70 years)

• Start at full replacement dose of 1.6 mcg/kg/day based on ideal body weight 1, 2, 4
• This typically translates to 75-100 mcg/day for women and 100-150 mcg/day for men 5
• Full-dose initiation is safe and reaches euthyroidism faster than low-dose titration (13 vs 1 patient euthyroid at 4 weeks in one trial) 4

For Elderly or Cardiac Patients (>70 years or cardiac disease)

• Start at 25-50 mcg/day to avoid precipitating angina or arrhythmias 1, 2, 3
• Increase by 12.5-25 mcg every 6-8 weeks based on TSH response 1
• Elderly patients with coronary disease are at increased risk of cardiac decompensation even with therapeutic doses 1

Administration Instructions

• Take as a single daily dose on an empty stomach, one-half to one hour before breakfast with a full glass of water 3
• Separate from interfering medications by at least 4 hours, including iron supplements, calcium supplements, and antacids 3
• Consistent timing and administration method are critical for stable absorption 6, 7

Monitoring Protocol

Initial Titration Phase

• Check TSH and free T4 every 6-8 weeks after initiating therapy or changing doses 1, 2
• This 6-8 week interval represents the time needed to reach steady state 1
• Adjust dose by 12.5-25 mcg increments based on TSH response 1
• Target TSH within the reference range (0.5-4.5 mIU/L) with normal free T4 1

Maintenance Phase

• Once TSH is stable at goal, monitor every 6-12 months or sooner if symptoms change 1, 2
• Free T4 can help interpret ongoing abnormal TSH levels during therapy, as TSH may take longer to normalize 1

Special Populations Requiring Modified Approach

Pregnant Women

• Levothyroxine requirements typically increase by 25-50% during pregnancy 1
• More aggressive TSH normalization is warranted, as subclinical hypothyroidism is associated with preeclampsia, low birth weight, and neurodevelopmental effects 1

Thyroid Cancer Patients

• TSH suppression may be intentional based on risk stratification 2
• Low-risk patients: target TSH 0.5-2 mIU/L 1
• Intermediate-to-high risk patients: target TSH 0.1-0.5 mIU/L 1
• Structural incomplete response: target TSH <0.1 mIU/L 1

Patients on Immunotherapy

• Thyroid dysfunction occurs in 6-20% of patients on immune checkpoint inhibitors 1
• Consider treatment even for subclinical hypothyroidism if fatigue or other symptoms are present 1
• Continue immunotherapy in most cases, as thyroid dysfunction rarely requires treatment interruption 1

Critical Pitfalls to Avoid

• Never start levothyroxine before ruling out adrenal insufficiency in patients with suspected central hypothyroidism - this can precipitate adrenal crisis 1, 3
• Do not treat based on a single elevated TSH value without confirmation, as 30-60% normalize spontaneously 1
• Avoid excessive dosing - approximately 25% of patients are unintentionally maintained on doses sufficient to fully suppress TSH, increasing risks for atrial fibrillation, osteoporosis, and cardiac complications 1, 3
• Do not use oral levothyroxine for myxedema coma - this life-threatening emergency requires IV formulation and ICU-level care 3, 8
• Monitor diabetic patients closely - levothyroxine increases metabolic clearance of glucose and may worsen glycemic control, requiring adjustment of antidiabetic medications 3

Risks of Overtreatment

Overtreatment with levothyroxine (TSH <0.1 mIU/L) significantly increases risk for:

• Atrial fibrillation and cardiac arrhythmias, especially in elderly patients 1, 3
• Osteoporosis and fractures, particularly in postmenopausal women 1, 3
• Increased cardiovascular mortality 1
• Accelerated bone loss with increased calcium and phosphorus excretion 3

Patient Counseling Points

• Inform patients that improvement may take several weeks after starting therapy 3
• Levothyroxine is generally lifelong therapy for replacement of thyroid hormone 3
• Not for weight loss - levothyroxine should not be used as primary or adjunctive therapy in weight control programs 3
• Report cardiac symptoms immediately including rapid or irregular heartbeat, chest pain, or shortness of breath 3
• Partial hair loss may occur rarely during the first few months but is usually temporary 3