Endocrine Abstracts

Introduction: There are a few hypothyroid patients who are refractory to standard thyroid hormone replacement treatment and require unexpectedly high doses of levothyroxine. In addition to clinical situations where hypothyroid patients are non-compliant (pseudomalbsortion), or where there is the possibility of excipient-induced disease exacerbation, therapeutic failure may be due to impaired absorption of the administered drug. The common approach to managing patients is to escalate the dose of levothyroxine until targeted TSH levels are achieved. We present a case of refractory hypothyroidism treated with intramuscular levothyroxine.

Case report: A 66 year old woman with hypothyroidism after a total thyroidectomy performed 8 years before, and in treatment with 250 μg per day of levothyroxine (3.67 μg/kg/day), presented at our outpatient clinic of endocrinology with a TSH level>150 μU/ml and FT4 0.40 ng/dl. We review pathological and non pathological causes of refractory hypothyroidism. We excluded concomitant gastrointestinal disease (H.Pylori infection, inflammatory bowel disease, celiac disease, lactose intolerance, atrophic body gastritis or gastrointestinal surgery), a poor conversion of T4 to T3, Addison’s disease, cystic fibrosis, nephrotic síndrome or amyloidosis. Also we revised pseudomalabsortion and drugs and dietary considerations that may affect levothyrxine absortion. After that, we switched to a generic levothyroxine with different bioavailability (without lactose and later, a liquid formulation). With both of them, first, FT4 reached normal values, but after 4 weeks TSH returned >150 μU/ml, FT4 0.24 ng/dl and FT3 0.5 pg/ml. We also tried with a combination T3/T4 therapy with the same result (an initial correction and again a severe hypothyroidism) Finally we performed a thyroxine absorption test: we administrated a single large dose of 1000 μg and blood samples were taken for baseline and at 60 min intervals up to 240min after the ingestión. Also we took blood samples at 24 and 48 h later. During the test TSH values remains stable and FT4 only rose up to 0.43 ng/dl. At this point we started treatment with intramuscular levothyroxine, 500 mcg per week. Her TSH and FT4 levels became normal. Currently the latest values are a TSH 2.33 μU/ml, FT4 1.29 ng/dl and FT3 2.4 pg/ml.

Conclusion: This is a case of refractary hypothyrodism due an isolated levotiroxine malabsortion. Intramuscular levothyroxine can be an effective alternative.