Levothyroxine Intolerance: Alternative Approach

Levothyroxine (LT4) replacement is the mainstay Rx of Hypothyroidism. LT4 is generally well tolerated but there have been some case reports suggesting adverse drug reactions and in 2020 self-reported multicenter retrospective chart review showed incidence of LT4 Intolerance to be ~ 0.3%. Through this article we present two different cases where patients have self-reported intolerance to LT4 therapy w/ different approach to their successful management other than desensitization previously detailed in case reports.

Case Description:

C1: 61Y F admitted for upper GI bleed & on workup found to have hypothyroidism w/ TSH of 92.5 and fT3 < 0.2 & fT4 < 0.1. Pt was diagnosed w/ Hashimoto's Disease 15 Yr ago & treated with LT4 including both generic & brand name. She experienced lethargy, hives, myalgia & anasarca and discontinued the medication. Despite several trials, she remained symptomatic and was therefore started on Desiccated Thyroid Extract (DTE) which resolved her symptoms. Literature review showed different approaches to desensitization & some evidence suggestive of possible dye allergy. Our patient was initiated on a trial of IV LT4 while inpatient, she was able to tolerate w/o side effects. Since she could tolerate IV, intolerance to dye was hypothesized. Pt was later successfully transitioned from IV LT4 to PO LT4 50 mcg pills (dye free).

C2: 57Y F admitted for SVT and on was found to be hypothyroid w/ TSH of 31.976 & fT4 of 0.58. She had been diagnosed w/ Graves' disease in 2006 & had underwent RAI. She experienced SOB & Hives with LT4, which persisted despite multiple attempts. She had been stable on DTE since 2008. However, she reports intermittent episodes of tachycardia, anxiety & heat intolerance w/ frequent fluctuation in dose. For ~ 6 months her TFT has been fluctuating more frequently causing multiple episodes of arrhythmia & hospitalization. She hasn't taken any replacement for a few weeks. Trial of LT4 50 mcg PO Daily was again used w/ success. Dose was adjusted & she was safely d/ced home.

Discussion:

Hypothyroidism has a prevalence of ~ 5% in the general population treated w/ thyroid hormone replacement. LT4 is the most common prescribed therapy. Other therapies include: LT4 + liothyronine(T3) and desiccated thyroid extract (DTE). DTE is not recommended b/c of high active hormone ratio, ↑ risk for thyrotoxicosis. LT4 + T3 combination is for pts w/ persistent symptoms on appropriate LT4.

There are no specific guidelines for Rx of pts w/ LT4 intolerance. Different desensitization methods are suggested by case reports. We suggest trial of dye free pill form though care for such patients should be individualized.