Abstract
INTRODUCTION: Allergic reaction to levothyroxine (LT4) is a very rare condition and has been reported mostly with oral levothyroxine. Here we present allergic reaction to intravenous (IV) LT4 in a patient with primary hypothyroidism unresponsive to oral therapy. CLINICAL CASE: A 51-year-old woman with primary hypothyroidism presented with profound fatigue, hair loss, constipation, hoarseness, and facial edema. Physical examination revealed bradycardia, dry pale skin, and hyporeflexia. She had hypothyroidism for 15 years and remained euthyroid for 12 years on LT4 tablets. Three years ago, she developed treatment resistance despite gradual dose escalation. Potential drug interactions, timing, and compliance were reviewed, with no issues identified. LT4 formulations free of lactose, confectioners’ sugar, gluten, sucrose, and other additives were tried first, followed by adjunctive liothyronine sodium, but no response was observed. An allergic reaction occurred after the first dose of liquid LT4, presenting with urticarial rash and facial angioedema. Current medications were LT4 po 350 mcg (5 mcg/kg/day), acetylsalicylic acid 100 mg, venlafaxine 150 mg, atorvastatin 10 mg, famotidine 40 mg. Her TSH was 128.61 mIU/L, fT4 0.37 ng/dL and fT3 1.84 pg/mL. Renal functions, serum electrolytes, and liver enzymes were normal. A 1000 mcg LT4 absorption test was consistent with malabsorption. She had no symptoms of malabsorptive disease. Malabsorption work-up, including stool elastase, steatocrit, calprotectin, celiac serology, parasitological tests and anti-parietal cell antibodies was negative. Duodenal biopsy showed no features of celiac disease. Helicobacter pylori was positive, but eradication therapy was discontinued due to generalized urticarial rash. LT4 dosage was increased to 10 mcg/kg/day. After 15 days, the patient remained overtly hypothyroid, and weekly IV LT4 200 mcg was initiated. During the first infusion, she developed anaphylaxis with facial angioedema and dyspnea at 20th min, which resolved after emergency treatment. Immunology and allergy consultation resulted in a plan for desensitization. With premedication (glucocorticoid, antihistamine, leukotriene receptor antagonist, acetylsalicylic acid), a 12-step desensitization protocol was initiated. Sessions 2–3 caused immediate throat pruritus and dyspnea; sessions 4 and 7 caused non-immediate flushing and throat irritation. Subsequent sessions were tolerated, allowing simplification to a single-bag protocol and reduced premedication. At the end of the initial 3 months, the dose was increased to 400 mcg/week. Treatment modifications, hormone levels, and current regimen are shown in Table 1. CONCLUSION: Patients with primary hypothyroidism unresponsive to oral therapy may be supported with IV treatment; however, it should be kept in mind that allergic reaction may develop with IV LT4, especially in a patient with a previous history of allergy to another form of the drug. [Figure: see text]