Falsely Elevated Serum Thyrotropin (TSH) in Newborn Infants: Transfer from Mothers to Infants of a Factor Interfering in the TSH Radioimmunoassay

Abstract

In a TSH screening program for congenital hypothyroidism we detected seven newborn infants with normal plasma T4 and T3 levels but high immunoassayable TSH. Similar findings were obtained in their mothers. Serial plasma dilution curves, with and without the addition of normal rabbit serum to the samples, showed that the result of TSH assay performed with antihuman TSH rabbit antiserum was falsely elevated in mothers and infants by an interfering factor. Follow-up of the infants demonstrated that the falsely elevated plasma TSH levels returned to normal within the first 6 months of life. On the contrary, plasma TSH levels remained high in the mothers. These results suggested a placental transfer of maternal antibodies. Indeed, the analysis of the mothers anamnesis revealed that all had previously received injections of a microbial vaccine cultured on a rabbit lung-containing medium. We conclude that placental transfer of a maternal antirabbit factor may cause an artefactual hyperthyrotropinemia in the newborn and the incorrect diagnosis of neonatal hypothyroidism. This can be avoided by the addition of normal rabbit serum or immunoglobulin to the TSH RIA tubes.

Factitious Increase in Thyrotropin in a Neonate Caused by a Maternally Transmitted Interfering Substance

“…Interference in immunoassays has been the subject of several reviews (4 -10 ). Although there have been several reports of transient neonatal hypothyroidism in the literature (11)(12)(13)(14)(15), we believe that this case is unusual because the mother had not received any previous medications or iodide treatment and had no known exposure to animals, and the interfering substance could not be identified as being a heterophile antibody.…”

Persistent hyperthyrotropinaemia since the neonatal period in clinically euthyroid children

“…Analysis of the maternal serum should indicate if this has arisen from transplacental antibody interference [3,6,7]. In these circumstances the hyperthyrotropinaemia is usually transient.…”

“…In some this is indicative of an ectopic thyroid [4,5]. In others, the increased plasma TSH may be transient and of an unknown cause [8] or artefactual arising from the transplacental transfer of maternal antibodies [3,6,7].…”

Elevated thyroid‐stimulating hormone level in a euthyroid neonate caused by macro thyrotropin–IgG complex

“…The interference was caused by transfer from mothers to infants of a factor (anti‐rabbit IgG) affecting TSH radioimmunoassays that included anti‐human TSH raised in rabbits. Some of the mothers had previously received the injections of microbial vaccine that had been cultured on rabbit lung‐containing medium (9), and some had kept a rabbit as a pet (8). Some of the infants had been treated initially with l ‐thyroxine (8,9,11).…”