What is the next step in managing a patient with persistent hyperthyroid-stimulating hormone (TSH) elevation, currently at 48.72, despite treatment with Synthroid (levothyroxine) and normal free thyroxine (T4) levels, after being diagnosed with profound hypothyroidism?

From the Guidelines

The patient should increase their Synthroid (levothyroxine) dose to 88 mcg daily and have their TSH and free T4 rechecked in 6 weeks. The patient's thyroid function remains significantly abnormal despite current treatment, with a TSH of 48.72 (still very elevated) and free T4 at the lower end of normal at 0.73. The patient has not followed up with endocrinology as recommended, which is concerning given their history of severe hypothyroidism requiring ICU admission. According to the guidelines for managing immune-related adverse events, including hypothyroidism, as outlined in the Journal of Clinical Oncology 1, patients with symptomatic hypothyroidism or those with TSH levels persistently above 10 mIU/L should be considered for thyroid hormone supplementation.

Key Considerations

• The patient's current TSH level is significantly elevated, indicating inadequate thyroid hormone replacement.
• The previous dose increase to 75 mcg was insufficient to normalize thyroid function, as evidenced by the repeat TSH level of 48.72.
• Increasing to 88 mcg represents a reasonable step-up in dosage that should help lower TSH while monitoring for proper thyroid hormone levels, as suggested by the guideline's management approach for G2 hypothyroidism 1.
• The patient should be strongly encouraged to keep their rescheduled endocrinology appointment on March 6th, as specialized management is important for someone with such severe hypothyroidism.
• Untreated or undertreated hypothyroidism can lead to serious complications including myxedema coma, cardiovascular issues, and cognitive impairment, highlighting the importance of achieving proper thyroid hormone replacement and regular monitoring, as emphasized in the guidelines for G3-4 hypothyroidism management 1.

Monitoring and Follow-Up

• Regular monitoring of TSH and free T4 levels is essential to adjust the levothyroxine dose as needed and to prevent complications associated with hypothyroidism.
• The patient's response to the increased dose should be closely monitored, with adjustments made according to the guidelines for managing hypothyroidism in patients treated with immune checkpoint inhibitor therapy 1.

From the FDA Drug Label

The general aim of therapy is to normalize the serum TSH level TSH may not normalize in some patients due to in utero hypothyroidism causing a resetting of pituitary-thyroid feedback. Failure of the serum T4 to increase into the upper half of the normal range within 2 weeks of initiation of levothyroxine sodium therapy and/or of the serum TSH to decrease below 20 IU per litre within 4 weeks may indicate the patient is not receiving adequate therapy Assess compliance, dose of medication administered, and method of administration prior to increasing the dose of levothyroxine sodium

The patient's TSH level is 48.72, which is not normalized. Given that the patient's free T4 is 0.73, which is within the normal range, but the TSH is elevated, it suggests that the patient may not be receiving adequate therapy. The next step would be to assess compliance and consider increasing the dose of levothyroxine sodium, as the current dose may not be sufficient to normalize the TSH level 2.

From the Research

Patient's Condition

• The patient was hospitalized for altered mental status and found to be in profound hypothyroidism with a TSH level in the 90s.
• She was treated with IV levothyroxine and her repeat TSH was elevated at 39.48, with normal free T4.
• The patient's TSH level continued to be elevated, with a repeat TSH of 48.72 and free thyroxine at 0.73.

Treatment Considerations

• According to 3, the goal of treatment for hypothyroidism is to normalize signs and symptoms, as well as to achieve thyroid-stimulating hormone (TSH) concentrations within the reference range.
• The standard treatment for hypothyroidism is levothyroxine (LT4) monotherapy, with the biochemical treatment goal being a TSH level within the reference range (0.4-4.0 mU/L) 4.
• For patients with persistent symptoms despite optimal T4 treatment, a trial of liothyronine (LT3) added to LT4 may be considered, especially if polymorphism of the deiodinase 2 (D2) genes is documented 3.
• However, the use of LT3 in hypothyroidism remains controversial, and numerous randomized trials have failed to show a benefit of treatment regimens that combine LT3 with LT4 over LT4 monotherapy 5.

Management Options

• The patient's elevated TSH level despite treatment with levothyroxine suggests that her hypothyroidism is not adequately controlled.
• Increasing the dose of levothyroxine, as suggested by Dr. Khan, may be a reasonable next step, with the goal of achieving a TSH level within the reference range.
• However, if the patient's symptoms persist despite optimal T4 treatment, a trial of combination therapy with LT4 and LT3 may be considered, as suggested by 6.
• It is essential to carefully monitor the patient's TSH and free thyroxine levels, as well as her symptoms, to determine the best course of treatment.