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 with a history of total thyroidectomy due to medullary thyroid cancer should restart levothyroxine at a reduced dose of 50 mcg daily, targeting a TSH in the normal range (0.450-4.500 uIU/mL) as TSH suppression is not appropriate for medullary thyroid cancer patients, according to the guidelines for medullary carcinoma 1. The severely elevated TSH (71.7 uIU/mL) and low T4 levels after 3 weeks off medication confirm hypothyroidism, which is expected after total thyroidectomy.

• The previous dose of 75 mcg was causing subclinical hyperthyroidism with suppressed TSH (0.055 uIU/mL), which is not desired in medullary thyroid cancer patients, as C cells lack TSH receptors and TSH suppression is not beneficial 1.
• After starting the 50 mcg dose, thyroid function tests should be repeated in 6-8 weeks, then adjust as needed, to ensure the patient's TSH levels are within the normal range.
• No thyroid imaging is necessary since the patient has had a total thyroidectomy, making functional thyroid tissue unlikely.
• However, serum calcitonin and carcinoembryonic antigen (CEA) levels should be monitored regularly to detect medullary thyroid cancer recurrence, as these are more appropriate tumor markers than imaging for this specific cancer type.
• The patient should take levothyroxine on an empty stomach, 30-60 minutes before breakfast, and avoid calcium, iron supplements, and certain foods within 4 hours of taking the medication to ensure proper absorption.

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.
• To adjust the levothyroxine dosage, a decision tree can be used to estimate the dose adjustment and reduce the time to euthyroidism, taking into account the patient's characteristics and thyroid-stimulating hormone values 4.
• The standard approach to levothyroxine replacement in obese and non-obese females after thyroidectomy is imprecise, and the dose required to achieve euthyroidism may vary greatly among individuals 5.
• A regression equation can be used to predict the initiated replacement dose of levothyroxine immediately following total thyroidectomy, taking into account the patient's body weight, age, and other factors 6.

Follow-up Thyroid Imaging

• There is no direct evidence in the provided studies to suggest a specific follow-up thyroid imaging modality for this patient.
• However, considering the patient's history of medullary cancer of the thyroid, follow-up imaging may be necessary to monitor for any potential recurrence or metastasis.
• The choice of imaging modality, such as ultrasound, CT, or MRI, would depend on the patient's specific clinical situation and the preferences of the treating physician.

Levothyroxine Dose Adjustment

• The patient's current TSH level is 71.700 uIU/mL, indicating severe hypothyroidism, and the levothyroxine dose may need to be increased to achieve euthyroidism 3.
• The adequate dose of levothyroxine for patients who have undergone total thyroidectomy for differentiated thyroid cancer is uncertain, but it may be estimated based on body weight, BMI, and age 7.
• A higher BMI may be related to a lower levothyroxine dose, especially in younger patients, and considering body weight, BMI, and age in estimating levothyroxine doses might help to achieve the target TSH level promptly 7.