What is the appropriate management for a patient with a history of total thyroidectomy due to medullary thyroid cancer, presenting with severe hypothyroidism, characterized by elevated Thyroid-Stimulating Hormone (TSH) levels and low thyroid hormone levels, after a 3-week suspension of Levothyroxine (thyroxine)?

From the Guidelines

The patient should immediately restart levothyroxine therapy at their previous dose of 75 mcg daily to address the severe hypothyroidism resulting from the 3-week medication suspension. This decision is based on the need to promptly correct the hypothyroid state and prevent further metabolic complications, as indicated by significantly elevated TSH levels and low thyroid hormone levels [ 1 ]. After restarting treatment, TSH and free T4 levels should be monitored in 6-8 weeks to determine if the dosage is appropriate. If TSH remains elevated or T4 levels are still low, the levothyroxine dose should be increased in increments of 12.5-25 mcg until optimal thyroid function is achieved, keeping in mind that the goal is to maintain TSH within the normal range, as TSH suppression is not appropriate for medullary thyroid cancer patients due to the lack of TSH receptors on C cells [ 1 ].

Key Considerations

• The patient's history of medullary thyroid cancer following total thyroidectomy necessitates careful management to prevent recurrence and ensure adequate thyroid hormone replacement.
• Monitoring of TSH and free T4 levels is crucial to adjust the levothyroxine dose appropriately and maintain optimal thyroid function.
• A neck ultrasound is recommended to evaluate for any cancer recurrence or metastasis, given the patient's history of medullary thyroid cancer.

Treatment Approach

• Restart levothyroxine at 75 mcg/day and monitor TSH and T4 levels in 6-8 weeks.
• Adjust the levothyroxine dose as necessary to maintain TSH within the normal range.
• Consider a neck ultrasound to evaluate for recurrence or metastasis due to the history of thyroid cancer, as part of a comprehensive follow-up plan [ 1 ].

From the FDA Drug Label

Many drugs and physiologic conditions affect the binding of thyroid hormones to serum proteins [see Drug Interactions (7)] . Thyroid hormones do not readily cross the placental barrier [see Use in Specific Populations Error! Hyperlink reference not valid.] Elimination Metabolism T4 is slowly eliminated (see Table 10). The major pathway of thyroid hormone metabolism is through sequential deiodination. Approximately 80% of circulating T3 is derived from peripheral T4 by monodeiodination The liver is the major site of degradation for both T4 and T3, with T4 deiodination also occurring at a number of additional sites, including the kidney and other tissues. Approximately 80% of the daily dose of T4 is deiodinated to yield equal amounts of T3 and reverse T3 (rT3). T3 and rT3 are further deiodinated to diiodothyronine Thyroid hormones are also metabolized via conjugation with glucuronides and sulfates and excreted directly into the bile and gut where they undergo enterohepatic recirculation. Excretion Thyroid hormones are primarily eliminated by the kidneys. A portion of the conjugated hormone reaches the colon unchanged and is eliminated in the feces. Approximately 20% of T4 is eliminated in the stool Urinary excretion of T4 decreases with age.

The patient should be restarted on levothyroxine at a dose of 75 mcg/day, which is the previous dose they were taking.

• The dosage may need to be adjusted based on TSH and T4 levels.
• A common strategy is to start with the previous dose and reassess in 6-8 weeks.
• If TSH remains elevated or if T4 levels do not normalize, the dosage can be increased in increments (typically 12.5 to 25 mcg) until the desired levels are achieved.
• Follow-up should include monitoring TSH and free T4 levels approximately 6-8 weeks after restarting therapy to assess the adequacy of treatment and make further adjustments as necessary 2.
• Consider neck ultrasound to evaluate for recurrence or metastasis due to the history of thyroid cancer.
• The patient should be informed that it may take several weeks before they notice an improvement in symptoms and that levothyroxine sodium tablets should not be used as a primary or adjunctive therapy in a weight control program 2.
• The patient should also be informed that partial hair loss may occur rarely during the first few months of levothyroxine sodium tablets therapy, but this is usually temporary 2.

From the Research

Treatment Approach

• The patient should be restarted on levothyroxine, considering the previous dosage of 75 mcg/day, with careful monitoring due to the recent suspension and current lab results indicating significant hypothyroidism 3, 4.
• The dosage may need to be adjusted based on TSH and T4 levels, with a common strategy being to start with the previous dose and reassess in 6-8 weeks 4.
• If TSH remains elevated or if T4 levels do not normalize, the dosage can be increased in increments (typically 12.5 to 25 mcg) until the desired levels are achieved 4.

Monitoring and Follow-Up

• Follow-up should include monitoring TSH and free T4 levels approximately 6-8 weeks after restarting therapy to assess the adequacy of treatment and make further adjustments as necessary 4.
• Consideration should be given to the patient's individual needs, including potential adjustments for weight or hormonal changes, concomitant medical conditions, and medications that may affect levothyroxine therapy 4, 5.

Imaging and Recurrence Evaluation

• A neck ultrasound is typically the first-line imaging modality to evaluate for residual thyroid tissue or lymphadenopathy associated with medullary thyroid cancer, given the patient's history of total thyroidectomy due to this condition 6.
• This imaging can help assess for any retained tissue or metastatic disease, guiding further management and follow-up 6.

Levothyroxine Therapy Considerations

• The goal of levothyroxine therapy is to achieve a euthyroid state, with normalization of serum TSH levels, although some patients may remain symptomatic despite normalized TSH levels 5, 7.
• The use of combination therapy with levothyroxine and liothyronine may be considered in patients who remain symptomatic despite optimized levothyroxine therapy, although current evidence does not consistently support its benefit 7.