What are the effects of initiating thyroid hormone replacement therapy (thyroid medication)?

From the Guidelines

Initiating thyroid hormone replacement therapy can have significant effects on patients, particularly older adults, with a substantial increase in prescriptions and treatment initiation at lower TSH levels over time. The effects of initiating thyroid hormone replacement therapy are multifaceted, with evidence suggesting a rise in treatment initiation, especially among older adults 1.

Key Considerations

• The annual number of dispensed prescriptions of levothyroxine sodium in the United States increased by 42% over a 5-year period 1, indicating a growing trend in thyroid hormone replacement therapy.
• A retrospective cohort study in the United Kingdom found that the median TSH level at the time of first levothyroxine prescription decreased from 8.7 to 7.9 mIU/L between 2001 and 2009 1, suggesting that treatment is being initiated at lower TSH levels.
• Older adults are more likely to initiate thyroid hormone therapy, with persons aged 85 years or older being more than twice as likely as those aged 65 to 69 years to begin therapy 1.

Clinical Implications

• Clinicians should be cautious when initiating thyroid hormone replacement therapy, considering the potential risks and benefits, particularly in asymptomatic patients.
• The high number of prescriptions for levothyroxine dispensed in the United States, combined with the low prevalence of overt hypothyroidism and hyperthyroidism, suggests that many asymptomatic persons may be receiving treatment 1.
• Regular monitoring of TSH levels and adjustment of medication doses are crucial to ensure optimal treatment outcomes and minimize potential adverse effects.

From the FDA Drug Label

They should immediately report during the course of therapy any signs or symptoms of thyroid hormone toxicity, e.g., chest pain, increased pulse rate, palpitations, excessive sweating, heat intolerance, nervousness, or any other unusual event. In case of concomitant diabetes mellitus, the daily dosage of antidiabetic medication may need readjustment as thyroid hormone replacement is achieved If thyroid medication is stopped, a downward readjustment of the dosage of insulin or oral hypoglycemic agent may be necessary to avoid hypoglycemia. Initiating thyroid replacement therapy may cause increases in insulin or oral hypoglycemic requirements Worsening of diabetic control:Therapy in patients with diabetes mellitus may worsen glycemic control and result in increased antidiabetic agent or insulin requirements.

The effects of initiating thyroid hormone replacement therapy include:

• Thyroid hormone toxicity: signs or symptoms such as chest pain, increased pulse rate, palpitations, excessive sweating, heat intolerance, nervousness
• Effects on diabetes management: potential need for readjustment of antidiabetic medication, increased risk of hypoglycemia if thyroid medication is stopped
• Increased insulin or oral hypoglycemic requirements: due to initiation of thyroid replacement therapy
• Worsening of diabetic control: potential increase in antidiabetic agent or insulin requirements 2, 2, 3

From the Research

Effects of Initiating Thyroid Hormone Replacement Therapy

The effects of initiating thyroid hormone replacement therapy can be understood by examining the available evidence on levothyroxine treatment.

• Levothyroxine sodium monotherapy is the preparation of choice in most patients with hypothyroidism, providing uniform levels of both thyroxine and triiodothyronine in the circulation without diurnal variation 4.
• The optimal daily levothyroxine sodium dose may be determined according to serum TSH level at the time of diagnosis of primary hypothyroidism, with a normal thyrotropin (TSH) level of 1-2 mU/L considered the determinant of optimal daily levothyroxine sodium dose in patients with primary hypothyroidism 4.
• Initial administration of close to the full calculated dose of levothyroxine sodium is appropriate for younger patients, while the elderly and patients with a history of coronary artery disease should start with a low dose and gradually titrate to the full calculated dose 4, 5, 6.
• Levothyroxine sodium can and should be continued in patients receiving treatment for coronary artery disease, but even minor over-replacement during initial titration should be avoided due to the risk of cardiac events 4.
• Chronic over-replacement may induce osteoporosis, particularly in postmenopausal women, and should also be avoided 4.

Treatment Monitoring and Adjustment

• Treatment monitoring is based mainly on blood TSH assay, with dose adjustment considered after 6 to 12 weeks given the long half-life of levothyroxine 5.
• Certain drugs, such as iron and calcium, reduce the gastrointestinal absorption of levothyroxine, while enzyme inducers reduce its efficacy 5.
• Symptom relief and normalized thyroid-stimulating hormone levels are achieved with levothyroxine replacement therapy, started at 1.5 to 1.8 mcg per kg per day 6.

Special Considerations

• Patients older than 60 years or with known or suspected ischemic heart disease should start at a lower dosage of levothyroxine (12.5 to 50 mcg per day) 5, 6.
• Women with hypothyroidism who become pregnant should increase their weekly dosage by 30% up to nine doses per week, followed by monthly evaluation and management 6.
• Most patients with subclinical hypothyroidism do not benefit from treatment unless the thyroid-stimulating hormone level is greater than 10 mIU per L or the thyroid peroxidase antibody is elevated 5, 6.