What is the appropriate levothyroxine (thyroid hormone replacement therapy) dosage adjustment for a patient with a history of total thyroidectomy due to medullary thyroid cancer, who has developed hyperthyrotropinemia (elevated Thyroid-Stimulating Hormone (TSH)) and hypothyroxinemia (low thyroxine (T4)) after suspending levothyroxine for 3 weeks?

From the Guidelines

The patient should restart levothyroxine at a reduced dose of approximately 50 mcg daily, as the previous dose of 75 mcg was likely excessive and caused iatrogenic hyperthyroidism, as evidenced by the suppressed TSH of 0.055 uIU/mL before suspension 1. After the 3-week suspension, the patient has developed severe hypothyroidism with a markedly elevated TSH of 71.7 uIU/mL and low T4 levels, which is expected given their history of total thyroidectomy for medullary thyroid cancer. Some key points to consider in the management of this patient include:

• The patient's history of total thyroidectomy for medullary thyroid cancer, which means there is no thyroid tissue to image, making thyroid imaging unnecessary 1.
• The need to monitor thyroid function tests in 6-8 weeks after restarting the reduced dose, then adjust as needed to achieve a TSH in the normal range (approximately 0.5-4.5 uIU/mL), as TSH suppression is not appropriate in patients with medullary thyroid cancer due to the lack of TSH receptors on C cells 1.
• Regular TSH monitoring every 3-6 months is recommended once stable, with dose adjustments made in 12.5-25 mcg increments as needed.
• It is crucial to keep the TSH level in the normal range, as TSH suppression is not the goal in patients with medullary thyroid cancer, unlike in other types of thyroid cancer 1. The patient's previous dose of 75 mcg was causing iatrogenic hyperthyroidism, and the reduced dose of 50 mcg is expected to help achieve a normal TSH level, improving the patient's quality of life and reducing the risk of morbidity and mortality associated with both hypothyroidism and hyperthyroidism.

From the FDA Drug Label

The dosage of levothyroxine sodium tablets for hypothyroidism or pituitary TSH suppression depends on a variety of factors including: the patient's age, body weight, cardiovascular status, concomitant medical conditions (including pregnancy), concomitant medications, co-administered food and the specific nature of the condition being treated [see Dosage and Administration, Warnings and Precautions (5), and Drug Interactions (7)] . For adult patients with primary hypothyroidism, titrate until the patient is clinically euthyroid and the serum TSH returns to normal [see Dosage and Administration] For secondary or tertiary hypothyroidism, serum TSH is not a reliable measure of levothyroxine sodium dosage adequacy and should not be used to monitor therapy. Use the serum free-T4 level to titrate levothyroxine sodium tablets dosing until the patient is clinically euthyroid and the serum free-T4 level is restored to the upper half of the normal range [see Dosage and Administration]

The patient has a history of total thyroidectomy due to medullary cancer of thyroid, which suggests secondary or tertiary hypothyroidism. Given the patient's low T4 and high TSH after suspending levothyroxine for 3 weeks, the dosage of levothyroxine should be adjusted. The patient was previously taking levothyroxine 75 mg, which is likely an error, as the typical dosage is in micrograms (mcg), not milligrams (mg). Assuming the patient was taking 75 mcg of levothyroxine, the dosage may need to be increased. However, the exact dosage adjustment cannot be determined without further information. It is recommended to titrate the dosage by 12.5 to 25 mcg increments every 4 to 6 weeks, as needed, until the patient is euthyroid, and the serum free-T4 level is restored to the upper half of the normal range. Follow-up thyroid function tests should be ordered to monitor the patient's response to the adjusted dosage. Thyroid imaging is not necessarily required at this time, but it may be considered in the future to monitor for any potential recurrence of thyroid cancer. The patient should be closely monitored for any signs of cardiovascular disease, as they are at risk for atrial fibrillation. 2

From the Research

Treatment and Levothyroxine Dosage Adjustment

• The patient has a history of total thyroidectomy due to medullary cancer of the thyroid and was taking levothyroxine 75 mg before the current thyroid panel results showed a TSH level of 71.700 uIU/mL and low thyroxine (T4) levels 3.
• The optimal dose of levothyroxine (LT4) is crucial to restore euthyroidism after total thyroidectomy, and an insufficient or excessive dosage may result in hypothyroidism or thyrotoxicosis 3.
• Most literature recommends an empirical dose of approximately 1.6 μg/kg of LT4, with subsequent changes according to thyroid function test results and assessments of the patient's symptoms 3.
• Factors such as lack of compliance, changes in LT4 formulation, dosage errors, increased serum levels of T4-binding globulin, body mass changes, and dietary habits may lead to the necessity of LT4 dose adjustments 3.
• The patient's current TSH level is high, indicating hypothyroidism, and the LT4 dose may need to be adjusted to achieve euthyroidism 4.

Follow-up Thyroid Imaging

• There is no direct evidence in the provided studies to suggest a specific follow-up thyroid imaging for this patient.
• However, the patient's history of total thyroidectomy and medullary cancer of the thyroid may require regular follow-up imaging to monitor for any potential recurrence or metastasis 5.
• The decision to order follow-up thyroid imaging should be based on the patient's individual clinical situation and the physician's professional judgment.

Adjusting Levothyroxine Dosage

• The patient's LT4 dose may need to be adjusted based on the current thyroid panel results and clinical assessment 6.
• A decision tree approach can be used to estimate LT4 dose adjustments and reduce the time to euthyroidism 5.
• The optimal LT4 dose for patients with immune checkpoint inhibitor-associated hypothyroidism is distinct from Hashimoto's thyroiditis, and a weight-based dose of 1.45 mcg/[kg·day] may be recommended 6.
• In obese patients, the LT4 dose per kg ideal body weight (IBW) may be higher than in nonobese patients, and a lower initial dose may be suggested 7.