Neonatal Graves’ Disease and Cholestatic Jaundice: Case Series and Review of the Literature
Affiliation(s)
1 University of Kansas Medical Center, Kansas City, USA. 2 Division of Pediatric Gastroenterology, St. Joseph’s Children Hospital, Paterson, USA. 3 Division of Pediatric Endocrinology, Upstate Medical Center, Golisano Children Hospital, Syracuse, USA.
1 University of Kansas Medical Center, Kansas City, USA. 2 Division of Pediatric Gastroenterology, St. Joseph’s Children Hospital, Paterson, USA. 3 Division of Pediatric Endocrinology, Upstate Medical Center, Golisano Children Hospital, Syracuse, USA.
ABSTRACT
Cholestatic jaundice and elevated liver enzymes are uncommon, but recognized, manifestations of neonatal thyrotoxicosis. Current guidelines for evaluation of cholestatic jaundice and reviews in Neonatology literature do not discuss hyperthyroidism in the differential diagnosis of cholestatic jaundice. We report two cases of neonatal thyrotoxicosis secondary to neonatal Graves’ disease that presented with cholestatic jaundice and elevated liver enzymes at birth. Early recognition of thyrotoxicosis as a cause of the hepatic disease in the neonate is crucial to prevent unnecessary diagnostic procedures and to initiate timely treatment.
Cholestatic jaundice and elevated liver enzymes are uncommon, but recognized, manifestations of neonatal thyrotoxicosis. Current guidelines for evaluation of cholestatic jaundice and reviews in Neonatology literature do not discuss hyperthyroidism in the differential diagnosis of cholestatic jaundice. We report two cases of neonatal thyrotoxicosis secondary to neonatal Graves’ disease that presented with cholestatic jaundice and elevated liver enzymes at birth. Early recognition of thyrotoxicosis as a cause of the hepatic disease in the neonate is crucial to prevent unnecessary diagnostic procedures and to initiate timely treatment.
KEYWORDS
Neonate, Graves’ Disease, Thyrotoxicosis, Hyperthyroidism, Cholestasis, Hepatitis, Jaundice, Conjugated Hyperbilirubinemia
Neonate, Graves’ Disease, Thyrotoxicosis, Hyperthyroidism, Cholestasis, Hepatitis, Jaundice, Conjugated Hyperbilirubinemia
Cite this paper
Almadhoun, O. , Rivera-Penera, T. and Lipeski, L. (2015) Neonatal Graves’ Disease and Cholestatic Jaundice: Case Series and Review of the Literature. Open Journal of Pediatrics, 5, 179-184. doi: 10.4236/ojped.2015.52027.
Almadhoun, O. , Rivera-Penera, T. and Lipeski, L. (2015) Neonatal Graves’ Disease and Cholestatic Jaundice: Case Series and Review of the Literature. Open Journal of Pediatrics, 5, 179-184. doi: 10.4236/ojped.2015.52027.
References
[1] Ramsay, I., Kaur, S. and Krassas, G. (1983) Thyrotoxicosis in Pregnancy: Results of Treatment by Antithyroid Drugs Combined with T4. Clinical Endocrinology (Oxford), 18, 73-85.
http://dx.doi.org/10.1111/j.1365-2265.1983.tb03188.x [2] McKenzie, J.M. and Zakarija, M. (1992) Fetal and Neonatal Hyperthyroidism and Hypothyroidism Due to Maternal TSH Receptor Antibodies. Thyroid, 2, 155-159.
http://dx.doi.org/10.1089/thy.1992.2.155 [3] Sunshine, P., Kusumoto, H. and Kriss, J.P. (1965) Survival Time of Circulating Long-Acting Thyroid Stimulator in Neonatal Thyrotoxicosis: Implications for Diagnosis and Therapy of the Disorder. Pediatrics, 36, 869-876. [4] Smallridge, R.C., Wartofsky, L., Chopra, I.J., Marinelli, P.V., Broughton, R.E., Dimond, R.C., et al. (1978) Neonatal Thyrotoxicosis: Alterations in Serum Concentrations of LATS-Protector, T4, T3, Reverse T3, and 3, 3’T2. Journal of Pediatrics, 93, 118-120.
http://dx.doi.org/10.1016/S0022-3476(78)80620-9 [5] Volpé, R., Ehrlich, R., Steiner, G. and Row, V.V. (1984) Graves’ Disease in Pregnancy Years after Hyperthyroidism with Recurrent Passive-Transfer Neonatal Graves’ Disease in Offspring. Therapeutic Considerations. American Journal of Medicine, 77, 572-578.
http://dx.doi.org/10.1016/0002-9343(84)90125-6 [6] Peleg, D., Cada, S., Peleg, A. and Ben-Ami, M. (2002) The Relationship between Maternal Serum Thyroid-Stimulating Immunoglobulin and Fetal and Neonatal Thyrotoxicosis. Obstetrics Gynecology, 99, 1040-1043.
http://dx.doi.org/10.1016/S0029-7844(02)01961-0 [7] Farrehi, C. (1968) Accelerated Maturity in Fetal Thyrotoxicosis. Clinical Pediatrics, 7, 134-137.
http://dx.doi.org/10.1177/000992286800700304 [8] Radetti, G., Zavallone, A., Gentili, L., Beck-Peccoz, P. and Bona, G. (2002) Foetal and Neonatal Thyroid Disorders. Minerva Pediatrica, 54, 383-400. [9] Zimmerman, D. (1999) Fetal and Neonatal Hyperthyroidism. Thyroid, 9, 727-733.
http://dx.doi.org/10.1089/thy.1999.9.727 [10] Daneman, D. and Howard, N.J. (1980) Neonatal Thyrotoxicosis: Intellectual Impairment and Craniosynostosis in Later Years. Journal of Pediatrics, 97, 257-259.
http://dx.doi.org/10.1016/S0022-3476(80)80487-2 [11] Zakarija, M., McKenzie, J.M. and Hoffman, W.H. (1986) Prediction and Therapy of Intrauterine and Late-Onset Neonatal Hyperthyroidism. The Journal of Clinical Endocrinology & Metabolism, 62, 368-71.
http://dx.doi.org/10.1210/jcem-62-2-368 [12] Hung, W. and Sarlis, N. (2004) Autoimmune and Non-Autoimmune Hyperthyroidism in Pediatric Patients. Pediatric Endocrinology Reviews, 2, 21-38. [13] Fong, T.L., McHutchison, J.G. and Reynolds, T.B. (1992) Hyperthyroidism and Hepatic Dysfunction. A Case Series Analysis. Journal of Clinical Gastroenterology, 14, 240-244.
http://dx.doi.org/10.1097/00004836-199204000-00010 [14] Skelton, M. (1955) Congenital Thyrotoxicosis, Hepatosplenomegaly and Jaundice in Two Infants of Exophthalmic Mothers. Archives of Disease in Childhood, 30, 460-464.
http://dx.doi.org/10.1136/adc.30.153.460 [15] Farber, S. and Craig, J. (1959) Clinical Pathological Conference: The Children’s Medical Center Boston, Mass. Journal of Pediatrics, 54, 829-837.
http://dx.doi.org/10.1016/S0022-3476(59)80154-2 [16] Hollinsworth, D. and Mabry, C.C. (1976) Congenital Graves Disease. Four Familial Cases with Long-Term Follow-Up and Perspective. American Journal of Diseases of Children, 130, 148-155.
http://dx.doi.org/10.1001/archpedi.1976.02120030038008 [17] Neal, P.R., Jansen, R.D., Lemons, J.A., Mirkin, L.D. and Schreiner, R.L. (1985) Unusual Manifestation of Neonatal Hyperthyroidism. American Journal of Perinatology, 2, 231-235.
http://dx.doi.org/10.1055/s-2007-999957 [18] Cove, D. and Johnston, P. (1985) Fetal Hyperthroidim: Experience of Treatment in Four Siblings. The Lancet, 1, 430-432.
http://dx.doi.org/10.1016/S0140-6736(85)91148-1 [19] Singer, J. (1977) Neonatal Thyrotoxicosis. Journal of Pediatrics, 91, 749-751.
http://dx.doi.org/10.1016/S0022-3476(77)81028-7 [20] Polak, M. (1998) Hyperthyroidism in Early Infancy: Pathogenesis, Clinical Features and Diagnosis with a Focus on Neonatal Hyperthyroidism. Thyroid, 12, 1171-1177.
http://dx.doi.org/10.1089/thy.1998.8.1171 [21] Page, D.V., Brady, K., Mitchell, J., Pehrson, J. and Wade, G. (1988) The Pathology of Intrauterine Thyrotoxicosis: Two Case reports. Obstetrics & Gynecology, 72, 479-481. [22] Beroukhim, R.S., Moon, T.D. and Felner, E.I. (2003) Neonatal Thyrotoxicosis and Conjugated Hyperbilirubinemia. Journal of Maternal-Fetal and Neonatal Medicine, 13, 426-428.
http://dx.doi.org/10.1080/jmf.13.6.426.428 [23] Dryden, C., Simpson, J.H., Hunter, L.E. and Jackson, L. (2007) An Unusual Cause of Neonatal Coagulopathy and Liver Disease. Journal of Perinatology, 27, 320-322.
http://dx.doi.org/10.1038/sj.jp.7211687 [24] Loomba-Albrecht, L.A., Bremer, A.A., Wong, A. and Philipps, A.F. (2012) Neonatal Cholestasis Caused by Hyperthyroidism. Journal of Pediatric Gastroenterology and Nutrition, 54, 433-434.
http://dx.doi.org/10.1097/MPG.0b013e318228f9a8 [25] Karpen, S.J. (2002) Update on the Etiologies and Management of Neonatal Cholestasis. Clinics in Perinatology, 29,159-180.
http://dx.doi.org/10.1016/S0095-5108(03)00069-1 [26] Venigalla, S. and Gourley, G.R. (2004) Neonatal Cholestasis. Seminars in Perinatology, 28, 348-355.
http://dx.doi.org/10.1053/j.semperi.2004.09.008 [27] Moyer, V., Freese, D.K., Whitington, P.F., Olson, A.D., Brewer, F., Colletti, R.B., et al. (2004) North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.Guideline for the Evaluation of Cholestatic Jaundice in infants: Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. Journal of Pediatric Gastroenterology and Nutrition, 39, 115-128.
http://dx.doi.org/10.1097/00005176-200408000-00001 [28] Myers, J.D., Brannon, E.S. and Holland, B.C. (1950) Correlative Study of the Cardiac Output and the Hepatic Circulation in Hyperthyroidism. Journal of Clinical Investigation, 29, 1069-1077.
http://dx.doi.org/10.1172/JCI102338 [29] Yao, J.D., Gross Jr., J.B., Ludwig, J. and Purnell, D.C. (1989) Cholestatic Jaundice and Hyperthyroidism. American Journal of Medicine, 86, 619-620.
http://dx.doi.org/10.1016/0002-9343(89)90398-7 [30] Hayashida, C.Y., Duarte, A.J.S., Sato, A.E. and E Yamashiro-Kanashiro.H. (1990) Neonatal Hepatitis and Lymphocyte Sensitization by Placental Transfer of Prpylthiouracil. Journal of Endocrinological Investigation, 13, 937-941.
http://dx.doi.org/10.1007/BF03349663 [31] Deidiker, R. and de Mello, D.E. (1996) Propythiouracil-Induced Fulminant Hepatitis: Case Report Review of the Literature. Pediatric Pathology & Laboratory Medicine, 16, 845-852.
http://dx.doi.org/10.3109/15513819609169310 [32] Foley, T. (1991) Maternally Transferred Thyroid Disease in the Infant: Recognition and Treatment. Advances in Perinatal Thyroidology, 299, 209-226.
http://dx.doi.org/10.1007/978-1-4684-5973-9_12
[1] Ramsay, I., Kaur, S. and Krassas, G. (1983) Thyrotoxicosis in Pregnancy: Results of Treatment by Antithyroid Drugs Combined with T4. Clinical Endocrinology (Oxford), 18, 73-85.
http://dx.doi.org/10.1111/j.1365-2265.1983.tb03188.x [2] McKenzie, J.M. and Zakarija, M. (1992) Fetal and Neonatal Hyperthyroidism and Hypothyroidism Due to Maternal TSH Receptor Antibodies. Thyroid, 2, 155-159.
http://dx.doi.org/10.1089/thy.1992.2.155 [3] Sunshine, P., Kusumoto, H. and Kriss, J.P. (1965) Survival Time of Circulating Long-Acting Thyroid Stimulator in Neonatal Thyrotoxicosis: Implications for Diagnosis and Therapy of the Disorder. Pediatrics, 36, 869-876. [4] Smallridge, R.C., Wartofsky, L., Chopra, I.J., Marinelli, P.V., Broughton, R.E., Dimond, R.C., et al. (1978) Neonatal Thyrotoxicosis: Alterations in Serum Concentrations of LATS-Protector, T4, T3, Reverse T3, and 3, 3’T2. Journal of Pediatrics, 93, 118-120.
http://dx.doi.org/10.1016/S0022-3476(78)80620-9 [5] Volpé, R., Ehrlich, R., Steiner, G. and Row, V.V. (1984) Graves’ Disease in Pregnancy Years after Hyperthyroidism with Recurrent Passive-Transfer Neonatal Graves’ Disease in Offspring. Therapeutic Considerations. American Journal of Medicine, 77, 572-578.
http://dx.doi.org/10.1016/0002-9343(84)90125-6 [6] Peleg, D., Cada, S., Peleg, A. and Ben-Ami, M. (2002) The Relationship between Maternal Serum Thyroid-Stimulating Immunoglobulin and Fetal and Neonatal Thyrotoxicosis. Obstetrics Gynecology, 99, 1040-1043.
http://dx.doi.org/10.1016/S0029-7844(02)01961-0 [7] Farrehi, C. (1968) Accelerated Maturity in Fetal Thyrotoxicosis. Clinical Pediatrics, 7, 134-137.
http://dx.doi.org/10.1177/000992286800700304 [8] Radetti, G., Zavallone, A., Gentili, L., Beck-Peccoz, P. and Bona, G. (2002) Foetal and Neonatal Thyroid Disorders. Minerva Pediatrica, 54, 383-400. [9] Zimmerman, D. (1999) Fetal and Neonatal Hyperthyroidism. Thyroid, 9, 727-733.
http://dx.doi.org/10.1089/thy.1999.9.727 [10] Daneman, D. and Howard, N.J. (1980) Neonatal Thyrotoxicosis: Intellectual Impairment and Craniosynostosis in Later Years. Journal of Pediatrics, 97, 257-259.
http://dx.doi.org/10.1016/S0022-3476(80)80487-2 [11] Zakarija, M., McKenzie, J.M. and Hoffman, W.H. (1986) Prediction and Therapy of Intrauterine and Late-Onset Neonatal Hyperthyroidism. The Journal of Clinical Endocrinology & Metabolism, 62, 368-71.
http://dx.doi.org/10.1210/jcem-62-2-368 [12] Hung, W. and Sarlis, N. (2004) Autoimmune and Non-Autoimmune Hyperthyroidism in Pediatric Patients. Pediatric Endocrinology Reviews, 2, 21-38. [13] Fong, T.L., McHutchison, J.G. and Reynolds, T.B. (1992) Hyperthyroidism and Hepatic Dysfunction. A Case Series Analysis. Journal of Clinical Gastroenterology, 14, 240-244.
http://dx.doi.org/10.1097/00004836-199204000-00010 [14] Skelton, M. (1955) Congenital Thyrotoxicosis, Hepatosplenomegaly and Jaundice in Two Infants of Exophthalmic Mothers. Archives of Disease in Childhood, 30, 460-464.
http://dx.doi.org/10.1136/adc.30.153.460 [15] Farber, S. and Craig, J. (1959) Clinical Pathological Conference: The Children’s Medical Center Boston, Mass. Journal of Pediatrics, 54, 829-837.
http://dx.doi.org/10.1016/S0022-3476(59)80154-2 [16] Hollinsworth, D. and Mabry, C.C. (1976) Congenital Graves Disease. Four Familial Cases with Long-Term Follow-Up and Perspective. American Journal of Diseases of Children, 130, 148-155.
http://dx.doi.org/10.1001/archpedi.1976.02120030038008 [17] Neal, P.R., Jansen, R.D., Lemons, J.A., Mirkin, L.D. and Schreiner, R.L. (1985) Unusual Manifestation of Neonatal Hyperthyroidism. American Journal of Perinatology, 2, 231-235.
http://dx.doi.org/10.1055/s-2007-999957 [18] Cove, D. and Johnston, P. (1985) Fetal Hyperthroidim: Experience of Treatment in Four Siblings. The Lancet, 1, 430-432.
http://dx.doi.org/10.1016/S0140-6736(85)91148-1 [19] Singer, J. (1977) Neonatal Thyrotoxicosis. Journal of Pediatrics, 91, 749-751.
http://dx.doi.org/10.1016/S0022-3476(77)81028-7 [20] Polak, M. (1998) Hyperthyroidism in Early Infancy: Pathogenesis, Clinical Features and Diagnosis with a Focus on Neonatal Hyperthyroidism. Thyroid, 12, 1171-1177.
http://dx.doi.org/10.1089/thy.1998.8.1171 [21] Page, D.V., Brady, K., Mitchell, J., Pehrson, J. and Wade, G. (1988) The Pathology of Intrauterine Thyrotoxicosis: Two Case reports. Obstetrics & Gynecology, 72, 479-481. [22] Beroukhim, R.S., Moon, T.D. and Felner, E.I. (2003) Neonatal Thyrotoxicosis and Conjugated Hyperbilirubinemia. Journal of Maternal-Fetal and Neonatal Medicine, 13, 426-428.
http://dx.doi.org/10.1080/jmf.13.6.426.428 [23] Dryden, C., Simpson, J.H., Hunter, L.E. and Jackson, L. (2007) An Unusual Cause of Neonatal Coagulopathy and Liver Disease. Journal of Perinatology, 27, 320-322.
http://dx.doi.org/10.1038/sj.jp.7211687 [24] Loomba-Albrecht, L.A., Bremer, A.A., Wong, A. and Philipps, A.F. (2012) Neonatal Cholestasis Caused by Hyperthyroidism. Journal of Pediatric Gastroenterology and Nutrition, 54, 433-434.
http://dx.doi.org/10.1097/MPG.0b013e318228f9a8 [25] Karpen, S.J. (2002) Update on the Etiologies and Management of Neonatal Cholestasis. Clinics in Perinatology, 29,159-180.
http://dx.doi.org/10.1016/S0095-5108(03)00069-1 [26] Venigalla, S. and Gourley, G.R. (2004) Neonatal Cholestasis. Seminars in Perinatology, 28, 348-355.
http://dx.doi.org/10.1053/j.semperi.2004.09.008 [27] Moyer, V., Freese, D.K., Whitington, P.F., Olson, A.D., Brewer, F., Colletti, R.B., et al. (2004) North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.Guideline for the Evaluation of Cholestatic Jaundice in infants: Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. Journal of Pediatric Gastroenterology and Nutrition, 39, 115-128.
http://dx.doi.org/10.1097/00005176-200408000-00001 [28] Myers, J.D., Brannon, E.S. and Holland, B.C. (1950) Correlative Study of the Cardiac Output and the Hepatic Circulation in Hyperthyroidism. Journal of Clinical Investigation, 29, 1069-1077.
http://dx.doi.org/10.1172/JCI102338 [29] Yao, J.D., Gross Jr., J.B., Ludwig, J. and Purnell, D.C. (1989) Cholestatic Jaundice and Hyperthyroidism. American Journal of Medicine, 86, 619-620.
http://dx.doi.org/10.1016/0002-9343(89)90398-7 [30] Hayashida, C.Y., Duarte, A.J.S., Sato, A.E. and E Yamashiro-Kanashiro.H. (1990) Neonatal Hepatitis and Lymphocyte Sensitization by Placental Transfer of Prpylthiouracil. Journal of Endocrinological Investigation, 13, 937-941.
http://dx.doi.org/10.1007/BF03349663 [31] Deidiker, R. and de Mello, D.E. (1996) Propythiouracil-Induced Fulminant Hepatitis: Case Report Review of the Literature. Pediatric Pathology & Laboratory Medicine, 16, 845-852.
http://dx.doi.org/10.3109/15513819609169310 [32] Foley, T. (1991) Maternally Transferred Thyroid Disease in the Infant: Recognition and Treatment. Advances in Perinatal Thyroidology, 299, 209-226.
http://dx.doi.org/10.1007/978-1-4684-5973-9_12