Increase in plasma thyrotropin levels in hypothyroid patients during treatment due to a defect in the commercial preparation

Abstract

Around mid-1995, the Molecular Endocrinology Laboratory of the Regional Hospital (Malaga, Spain) began detecting an increase in TSH levels in the serum of patients under study to control the treatment of hypothyroidism with levothyroxine. Over a period of 5 months, of a total of 467 hypothyroid patients treated with Levothyroid, 53% had TSH levels higher than 6 microU/mL. The reliability of the biochemical results was verified by duplicating 56 randomly chosen samples from all those with high TSH levels and by an external control performed in four different laboratories. The amount of levothyroxine in the tablets was analyzed by RIA, high performance liquid chromatography, and their iodine contents. The lowest levels of levothyroxine found in the 50 micrograms Levothyroid tablets were those determined by RIA, with a mean value of 32.3 micrograms, resulting in a 35.3% loss of activity. The mean value of levothyroxine found in these same tablets by high performance liquid chromatography was 39.3 micrograms, amounting to a 21.3% loss in activity. The iodine showed no significant loss in these tablets, with a mean experimental value of 48 micrograms. The commercial laboratory withdrew lot J from the market, the one in which these deficiencies were found.