How to manage hypothyroidism in a patient on nivolumab (Opdivo) with elevated TSH levels?

From the Guidelines

For a patient on nivolumab with elevated TSH levels, indicating hypothyroidism, hormone replacement therapy with levothyroxine should be initiated at a dose of 50-100 mg/day in symptomatic cases, and the dose should be increased over several weeks until thyroid-stimulating hormone levels normalize, as recommended by the most recent guidelines 1. The management of hypothyroidism in patients receiving nivolumab involves careful consideration of the symptoms and the severity of the condition.

• In symptomatic cases, the initiation of levothyroxine replacement therapy is crucial to manage symptoms and normalize TSH levels.
• The dose of levothyroxine should be adjusted based on the patient's response and TSH levels, with the goal of achieving normal thyroid function.
• Nivolumab therapy can generally continue without interruption, unless symptoms are severe (grade 3), in which case temporary interruption may be necessary, as indicated by the guidelines 1.
• Monitoring of thyroid function tests, including TSH and free T4, is essential to adjust the levothyroxine dose and to assess the patient's response to therapy.
• It is also important to note that thyroid dysfunction caused by checkpoint inhibitors like nivolumab can be permanent, and patients may require lifelong thyroid hormone replacement therapy, as suggested by clinical experience and guidelines 1. Key considerations in managing hypothyroidism in patients on nivolumab include:
• Prompt initiation of levothyroxine replacement therapy in symptomatic cases
• Close monitoring of thyroid function tests to adjust the levothyroxine dose
• Continuation of nivolumab therapy, unless severe symptoms necessitate temporary interruption
• Awareness of the potential for permanent thyroid dysfunction and the need for long-term thyroid hormone replacement therapy, as supported by the most recent and highest quality evidence 1.

From the FDA Drug Label

For adult patients with primary hypothyroidism, titrate until the patient is clinically euthyroid and the serum TSH returns to normal The recommended starting daily dosage of levothyroxine sodium tablets in adults with primary, secondary, or tertiary hypothyroidism is based on age and comorbid cardiac conditions, as described in Table 1 For patients at risk of atrial fibrillation or patients with underlying cardiac disease, start with a lower dosage and titrate the dosage more slowly to avoid exacerbation of cardiac symptoms. Dosage titration is based on serum TSH or free-T4

The patient is receiving nivolumab and has an elevated TSH level of 30.5 µIU/ml, indicating hypothyroidism. To manage hypothyroidism in this patient,

• Levothyroxine sodium tablets can be used as a replacement therapy.
• The dosage of levothyroxine sodium tablets should be individualized based on the patient's age, body weight, cardiovascular status, and other factors.
• The patient's serum TSH level should be monitored every 6 to 8 weeks after any change in dosage, and the dosage should be titrated until the patient is clinically euthyroid and the serum TSH returns to normal.
• It is essential to monitor the patient's clinical response and laboratory parameters, including serum TSH and free-T4 levels, to ensure adequate therapy 2.
• The starting dosage for adults with primary hypothyroidism is typically 1.6 mcg/kg/day, with some patients requiring a lower starting dose 2.
• Titrate dosage by 12.5 to 25 mcg increments every 4 to 6 weeks, as needed, until the patient is euthyroid 2.

From the Research

Managing Hypothyroidism in a Patient on Nivolumab with Elevated TSH Levels

• The patient's elevated TSH level of 30.5 µIU/ml indicates hypothyroidism, which is a common disorder due to inadequate thyroid hormone secretion 3.
• The symptoms of hypothyroidism are due to slow metabolism and polysaccharide accumulation in certain tissues, leading to symptoms such as constipation, fatigue, sensitivity to cold, weight gain, and hoarseness 3.
• The natural history of hypothyroidism depends on its cause, and in chronic autoimmune thyroiditis, hypothyroidism generally worsens over time 3.
• Treatment guidelines recommend levothyroxine therapy, and the adverse effects of levothyroxine are signs of thyrotoxicosis in case of overdose 3, 4.
• The optimal daily levothyroxine sodium dose may be determined according to serum TSH level at the time of diagnosis of primary hypothyroidism, and initial administration of close to the full calculated dose of levothyroxine sodium is appropriate for younger patients 4.
• In elderly patients and those with a history of coronary artery disease, the well-established approach of starting with a low dose and gradually titrating to the full calculated dose is always the best option 4, 5.
• Levothyroxine sodium can and should be continued in patients receiving treatment for coronary artery disease, and even minor over-replacement during initial titration of levothyroxine sodium 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.
• 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 5.
• 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.
• 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.

Considerations for Patients on Nivolumab

• There is no specific guidance on managing hypothyroidism in patients on nivolumab, but the general principles of managing hypothyroidism apply 3, 4, 5.
• Patients on nivolumab should be monitored for signs and symptoms of hypothyroidism, and levothyroxine replacement therapy should be started if necessary 3, 4, 5.
• The dosage of levothyroxine should be adjusted based on the patient's serum TSH level, and patients should be monitored for signs of thyrotoxicosis or over-replacement 3, 4, 5.