Advertisement

Journal of Endocrinological Investigation

, Volume 13, Issue 11, pp 937–941 | Cite as

Neonatal hepatitis and lymphocyte sensitization by placental transfer of propylthiouracil

  • C. Y. Hayashida
  • A. J. S. Duarte
  • A. E. Sato
  • E. H. Yamashiro-Kanashiro
Case Report

Abstract

A female newborn whose mother was taking propylthiouracil (PTU) for Graves’ disease, presented with transient thyrotoxicosis (serum triiodothyronine 1,710 ng/dl) and signs of acute hepatic injury. Jaundice and choluria were evident on her fourth day of life. Serum total bilirubin reached 14 mg/dl, with a direct fraction of 11 mg/dl. Serum alanine aminotransferase and aspartate aminotransferase showed moderate elevations (110 IU/I and 61.5 IU/I, respectively), as well as the alkaline prosphatase which increased to about twice the upper limit of normal. When incubated with PTU, the patient’s cultured peripheral lymphocytes underwent transformation to more than twice the values found in 2 controls, with a stimulation index (SI) of 3.19, compared to SI of 1.45 and 1.15 for the controls, suggesting a hypersensitivity mechanism involved in the hepatic injury. Although about 20 cases of PTU induced hepatic damage were reported in the medical literature, this is, as far as we know, the first description of neonatal liver injury probably caused by placental transfer of this drug.

Key-words

Propylthiouracil hepatitis maternal-fetal exchange lymphocyte transformation 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Cooper D.S. Antithyroid drugs. N.Engl. J.Med. 311: 1353, 1984.PubMedCrossRefGoogle Scholar
  2. 2.
    Marchant B., Brownlie B.E.W., Hart D.M., Horton P.W., Alexander W.D. The placental transfer of propylthiouracil, methimazole and Carbimazole. J. Clin. Endocrinol. Metab. 45: 1187, 1977.PubMedCrossRefGoogle Scholar
  3. 3.
    Milham S. Jr., Elledge W. Maternal methimazole and congenital defects in children. Teratology 5: 125, 1972.CrossRefGoogle Scholar
  4. 4.
    Mujtaba G., Burrow G.N. Treatment of hyperthyroidism in pregnancy with propylthiouracil and methimazole. Obstet. Gynecol. 46: 282, 1975.PubMedGoogle Scholar
  5. 5.
    Vitug A.C., Goldman J.M. Hepatotoxicity from antithyroid drugs. Hormone Res. 21: 229, 1985.PubMedCrossRefGoogle Scholar
  6. 6.
    Bloch C.A., Jenski L.J., Balistreri W.F., Dolan L.M. Propylthiouracil-associated hepatitis. Arch. Intern. Med. 145: 2129, 1985.PubMedCrossRefGoogle Scholar
  7. 7.
    Cofre C., Valdes E., Tapia A., Rodriguez J. Hepatitis colestasica secundaria a propiltiouracilo. Rev. Med. Chil. 114: 42, 1986.PubMedGoogle Scholar
  8. 8.
    Limage A., Ruffolo P.R. Propylthiouracil-induced fatal hepatic necrosis. Am. J. Gastroenterol. 82: 152, 1987.Google Scholar
  9. 9.
    Gardner D.F., Cruikshank D.P., Hays P.M., Cooper D.S. Pharmacology of propylthiouracil (PTU) in pregnant hyperthyroid women: correlation of maternal PTU concentrations with cord serum thyroid function tests. J. Clin. Endocrinol. Metab. 62: 217, 1986.PubMedCrossRefGoogle Scholar
  10. 10.
    Burrow G.N. Neonatal goiter after maternal propylthiouracil therapy. J. Clin. Endocrinol. Metab. 25: 403, 1965.PubMedCrossRefGoogle Scholar
  11. 11.
    Munro D.S., Dirmikis S.M., Humphries H, Smith T., Broadhead G.D. The role of thyroid stimulating immunoglobulins of Graves’s disease in neonatal thyrotoxicosis. Br. J. Obstet. Gynaecol. 85: 837, 1978.PubMedCrossRefGoogle Scholar
  12. 12.
    Zakarija M., Mackenzie J.M. Pregnancy-associated changes in the thyroid-stimulating antibody of Graves’ disease and the relationship to neonatal hyperthyroidism. J. Clin. Endocrinol. Metab. 57: 1036, 1983.PubMedCrossRefGoogle Scholar
  13. 13.
    Yagi H., Takeuchi M., Nagashima K.f Suzuki S., Kuroume T., Ilda Y., Konishi J., Endo K. Neonatal transient thyrotoxicosis resulting from maternal TSH-binding inhibitor immunoglobulins. J. Pediatr. 103: 591, 1983.PubMedCrossRefGoogle Scholar
  14. 14.
    Matsuda T., Momoi T., Akaishi K., Yagura T., Kasagi K., Endo K. Transient neonatal hyperthyroidism and maternal thyroid stimulating immunoglobulins. Arch. Dis. Child. 63: 205, 1988.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Greenberger N.J., Milligan F.D., DeGroot L.J., Isselbacher K.J. Jaundice and thyrotoxicosis in the absence of congestive heart failure. Am. J. Med. 36: 840, 1964.PubMedCrossRefGoogle Scholar
  16. 16.
    Mihas A.A., Holley P., Koff R.S., Hirschowitz B.I. Fulminant hepatitis and lymphocyte sensitization due to propylthioracil. Gastroenterology 70: 770, 1976.PubMedGoogle Scholar
  17. 17.
    Pacini F., Sridama V., Refetoff S. Multiple complications of propylthiouracil treatment: granulocytopenia, eosinophilia, skin reaction and hepatitis with lymphocyte sensitization. J. Endocrinol. Invest. 5: 403, 1982.PubMedCrossRefGoogle Scholar
  18. 18.
    Parker W.A. Propylthiouracil-induced hepatotoxicity. Clin. Pharm. 1: 471, 1982.PubMedGoogle Scholar
  19. 19.
    Parker L.N. Hepatitis and propylthiouracil. Ann. Intern. Med. 82: 288, 1975.CrossRefGoogle Scholar
  20. 20.
    Block C.A., Jenski L.J., Balistreri W.F., Dolan L.M. Propylthiouracil-associated hepatitis. Arch. Intern. Med. 145: 2129, 1985.CrossRefGoogle Scholar
  21. 21.
    Elkington S.G., Schreiber W.M., Conn H.O. Hepatic injury caused by L-alpha-methyldopa. Circulation 40: 589, 1969.PubMedCrossRefGoogle Scholar
  22. 22.
    Rodman J.S., Deutsch DJ., Gutman S.I. Methyldopa hepatitis. A report of six cases and review of the literature. Am.J. Med. 60: 941, 1976.PubMedCrossRefGoogle Scholar
  23. 23.
    Neuberger J., Kenna J.G., Aria K.N., Williams R. Antibody mediated hepatocyte injury in methyldopa induced hepatotoxicity. Gut 26: 1233, 1985.PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Jones H.M.R., Cummings A.J. A study of the transfer of methyldopa to the human foetus and newborn infant. Br. J. Clin. Pharmacol. 6: 432, 1978.PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Torres A.C., Tong M J., Chang K, Schweitzer I. Lymphocyte stimulation in alpha-methyldopa related hepatitis. Clin. Res. 24: 106A, 1976, (Abstract).Google Scholar
  26. 26.
    Ludwig J., Axelsen R. Drug effects on the liver. An updated tabular compilation of drugs and drug-related hepatic diseases. Dig. Dis. Sci. 23: 651, 1983.CrossRefGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 1990

Authors and Affiliations

  • C. Y. Hayashida
    • 1
  • A. J. S. Duarte
    • 2
  • A. E. Sato
    • 3
  • E. H. Yamashiro-Kanashiro
    • 2
  1. 1.Department of Medicine, Division of EndocrinologySchool of Medicine, São Paulo UniversitySão PauloBrasil
  2. 2.Immunogenetics and Experimental Transplantation LaboratorySchool of Medicine, São Paulo UniversityBrasil
  3. 3.Unit of NeonatologyHospital e Maternidade Leonor Mendes de BarrosSão PauloBrasil

Personalised recommendations