What are the prescription-related concerns for patients with hyperglycemia and severe hypothyroidism?

From the Guidelines

Patients with hyperglycemia and severe hypothyroidism should be managed with a combination of levothyroxine and insulin therapy, with metformin added as a second-line agent, as this approach has been shown to improve glycemic control and reduce morbidity and mortality 1. When managing severe hypothyroidism, it is essential to start with a low dose of levothyroxine (typically 25-50 mcg daily) and gradually increase every 2-4 weeks based on TSH and T4 levels until euthyroidism is achieved 1. For hyperglycemia management, insulin therapy should be initiated when blood glucose levels exceed 16.7 to 19.4 mmol/L (300 to 350 mg/dL) or greater, and/or HbA1c levels are 10% to 12%, especially if symptomatic or catabolic features are present 1. Some key points to consider when managing hyperglycemia and severe hypothyroidism include:

• Insulin therapy should not be delayed in patients not achieving glycemic goals 1
• Basal insulin may be initiated at 10 units or 0.1 to 0.2 units/kg of body weight 1
• Metformin can be added as a second-line agent to improve glycemic control 1
• Monitoring blood glucose levels more frequently during thyroid hormone replacement is crucial, as metabolic needs change 1
• Thyroid hormone increases cellular metabolism and can worsen hyperglycemia initially, so glucose-lowering therapy may need adjustment during thyroid treatment 1.

From the FDA Drug Label

5.5 Worsening of Diabetic Control

7.2 Antidiabetic Therapy

• Hyperglycemia: The FDA drug label warns that levothyroxine sodium tablets may cause worsening of diabetic control [ 2 ].
• Severe Hypothyroidism: Patients with severe hypothyroidism may be at risk for worsening of diabetic control when treated with levothyroxine [ 2 ].
• Key Considerations:
  • Patients with diabetes mellitus may require adjusted antidiabetic therapy when treated with levothyroxine [ 2 ].
  • Monitoring of blood glucose levels is recommended for patients with diabetes mellitus who are treated with levothyroxine [ 2 ].

From the Research

Hyperglycemic and Severe Hypothyroidism

• Hyperglycemia and hypothyroidism are two distinct medical conditions that can have significant effects on the body.
• There is limited research on the direct relationship between hyperglycemia and severe hypothyroidism, however, some studies suggest that metformin, a common treatment for hyperglycemia, may have an impact on thyroid function 3, 4.
• A study published in the Journal of Clinical Pharmacy and Therapeutics found that metformin reduced thyrotrophin levels in subjects with hypothyroidism, and the impact on insulin sensitivity and thyrotrophin was stronger in women simultaneously treated with levothyroxine than in women not receiving this hormone 3.
• Another study published in Minerva Endocrinologica found that adding metformin to the drug regimen of patients with thyroid cancer under suppressive therapy with levothyroxine was not useful to compensate for a 33% reduction in levothyroxine dose 4.

Treatment of Hypothyroidism

• Levothyroxine is the standard therapy for patients with hypothyroidism, and the goal of treatment is to achieve consistent maintenance of euthyroidism without the patient experiencing adverse events and negative health consequences of under- or overtreatment 5, 6.
• The dosage of levothyroxine can vary greatly and may be based on the amount of residual thyroid function retained by the patient, the body weight or lean body mass of the patient, and thyroid-stimulating hormone levels 5.
• Patients with concomitant medical conditions, such as hyperglycemia, may require dose adjustments of levothyroxine, and the majority of pregnant women require increased doses of levothyroxine 5, 6.

Management of Hypothyroidism

• Optimal treatment of hypothyroidism requires a partnership between patient and physician, with the physician tasked with vigilant appraisal of the patient's status based on a thorough clinical and laboratory assessment and appropriate adjustment of their levothyroxine therapy 5.
• Patients with hypothyroidism should be monitored regularly for signs and symptoms of thyroid dysfunction, and adjustments to their treatment plan should be made as needed 6.
• There is no evidence that population screening for hypothyroidism is beneficial, and diagnosis is based on blood levels of thyroid-stimulating hormone and free thyroxine 6.