Liothyronine

Name: LIOTHYRONINE
Class: Thyroid
Risk Factor: AM

Fetal Risk Summary

Liothyronine (T3) is a naturally occurring thyroid hormone produced by the mother and the fetus. It is used during pregnancy for the treatment of hypothyroidism (see also Levothyroxine and Thyroid). There is little or no transplacental passage of the hormone at physiologic serum concentrations (1,2 and 3). Limited placental passage of T3 to the fetus has been demonstrated following very large doses (4,5).

In a large prospective study, 34 mother-child pairs were exposed to liothyronine during the 1st trimester (6). No association between the drug and fetal defects was found. Maternal hypothyroidism itself has been reported to be responsible for poor pregnancy outcome (7). Others have not found this association, claiming that fetal development is not directly affected by maternal thyroid function (8).

Combination therapy with thyroid-antithyroid drugs was advocated at one time for the treatment of hyperthyroidism but is now considered inappropriate (see Propylthiouracil).

Breast Feeding Summary

Liothyronine (T3) is excreted into breast milk in low concentrations. The effect on the nursing infant is not thought to be physiologically significant, although at least one report concluded otherwise (9). An infant was diagnosed as athyrotic shortly after breast feeding was stopped at age 10 months (9). Growth was at the 97th percentile during breast feeding, but the bone age remained that of a newborn. Mean levels of T3 in breast milk during the last trimester (12 patients) and within 48 hours of delivery (22 patients) were 1.36 and 2.86 ng/mL, respectively. A 1978 study reported milk concentrations varying between 0.4 and 2.38 ng/mL (range 0.1–5 ng/mL) from the day of delivery to 148 days postpartum (10). No liothyronine was detected in a number of the samples. Levels in three instances, collected 16, 20, and 43 months postpartum, ranged from 0.68 to 4.5 ng/mL with the highest concentration measured at 20 months. From the 1st week through 148 days postdelivery, the calculated maximum amount of T3 that a nursing infant would have ingested was 2.1–2.6 µg/day, far less than the dose required to treat congenital hypothyroidism (10). However, the authors concluded that this was enough to mask the symptoms of the disease without halting its progression. In a study comparing serum T3 levels between 22 breast-fed and 29 formula-fed infants, significantly higher levels were found in the breast-feeding group (11). The levels, 2.24 and 1.79 ng/mL, were comparable to previous reports and probably were of doubtful clinical significance. A 1980 report described four exclusively breast-fed infants with congenital hypothyroidism who were diagnosed between the ages of 2 and 79 days (12). Breast feeding did not hinder making the diagnosis. Another 1980 research report evaluated clinical and biochemical thyroid parameters in 45 hypothyroid infants, 12 of whom were breast-fed (13). No difference was detected between the breast-fed and bottle-fed babies, leading to the conclusion that breast milk does not offer protection against the effects of congenital hypothyroidism. As reported in a 1985 paper, serum concentrations of T3 were similar in breast-fed and bottle-fed infants at 5, 10, and 15 days postpartum (14).

Japanese researchers found a T3 milk:plasma ratio of 0.36 (15). No correlation was discovered between serum T3 and milk T3 or total daily T3 excretion. Neither was there a correlation between milk T3 levels and milk protein concentration or daily volume of milk. They concluded that breast feeding has no influence on the pituitary-thyroid axis of normal babies. A Swedish investigation measured higher levels of T3 in milk 1–3 months after delivery as compared with T3 levels in early colostrum (16). The concentrations were comparable to the studies cited above.

In summary, liothyronine breast milk concentrations are too low to protect a hypothyroid infant completely from the effects of the disease. The levels are also too low to interfere with neonatal thyroid screening programs (14).

References

1. Grumbach MM, Werner SC. Transfer of thyroid hormone across the human placenta at term. J Clin Endocrinol Metab 1956;16:1392–5.
2. Kearns JE, Hutson W. Tagged isomers and analogues of thyroxine (their transmission across the human placenta and other studies). J Nucl Med 1963;4:453–61.
3. Fisher DA, Lehman H, Lackey C. Placental transport of thyroxine. J Clin Endocrinol Metab 1964;24:393–400.
4. Raiti S, Holzman GB, Scott RI, Blizzard RM. Evidence for the placental transfer of tri-iodothyronine in human beings. N Engl J Med 1967;277:456–9.
5. Dussault J, Row VV, Lickrish G, Volpe R. Studies of serum triiodothyronine concentration in maternal and cord blood: transfer of triiodothyronine across the human placenta. J Clin Endocrinol Metab 1969;29:595–606.
6. Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA:Publishing Sciences Group, 1977:388–400.
7. Potter JD. Hypothyroidism and reproductive failure. Surg Gynecol Obstet 1980;150:251–5.
8. Montoro M, Collea JV, Frasier SD, Mestman JH. Successful outcome of pregnancy in women with hypothyroidism. Ann Intern Med 1981;94:31–4.
9. Bode HH, Vanjonack WJ, Crawford JD. Mitigation of cretinism by breast-feeding. Pediatrics 1978;62:13–6.
10. Varma SK, Collins M, Row A, Haller WS, Varma K. Thyroxine, triiodothyronine, and reverse triiodothyronine concentrations in human milk. J Pediatr 1978;93:803–6.
11. Hahn HB Jr, Spiekerman AM, Otto WR, Hossalla DE. Thyroid function tests in neonates fed human milk. Am J Dis Child 1983;137:220–2.
12. Abbassi V, Steinour TA. Successful diagnosis of congenital hypothyroidism in four breast-fed neonates. J Pediatr 1980;97:259–61.
13. Letarte J, Guyda H, Dussault JH, Glorieux J. Lack of protective effect of breast-feeding in congenital hypothyroidism: report of 12 cases. Pediatrics 1980;65:703–5.
14. Franklin R, O'Grady C, Carpenter L. Neonatal thyroid function: comparison between breast-fed and bottle-fed infants. J Pediatr 1985;106:124–6.
15. Mizuta H, Amino N, Ichihara K, Harade T, Nose O, Tanizawa O, Miyai K. Thyroid hormones in human milk and influence on thyroid function of breast-fed babies. Pediatr Res 1983;17:468–71.
16. Jansson L, Ivarsson S, Larsson I, Ekman R. Tri-iodothyronine and thyroxine in human milk. Acta Paediatr Scand 1983;72:703–5.

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