Neonatal cholestasis caused by Graves’ disease：a case report and literature review

Neonatal cholestasis caused by Graves’ disease：a case report and literature review | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Neonatal cholestasis caused by Graves’ disease：a case report and literature review Yanhui Zhang, Lianshuang Liu, Yi Lu, Weiyuan Fang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7000759/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective Neonatal/Infantile cholestasis (NIC) is defined as an impairment in bile formation and/or flow presenting by the first year of age, typically within the first three months. Hyperthyroidism has been less frequently associated with this condition. Here, we reported a case of neonatal cholestasis caused by Graves' disease and reviewed relevant literatures to summarize its clinical characteristics, aim to enhance recognition and diagnosis of this disease promptly and precisely. Case presentation A 28-day-old female infant was admitted to our center, presented with jaundice, diarrhea, poor weight gain, and tachycardia. laboratory examinations showed cholestasis, hyperthyroidism and positive thyroid receptor antibody, confirming the diagnosis of neonatal Grave’s disease. After treatment with Propranolol and intravenous immunoglobulins (IVIG), the jaundice subsided and thyroid function returned to normal. Conclusions neonatal Graves’ disease must be included in the differential diagnosis of cholestasis, particularly in infants whose mothers have Graves’ disease or a history of thyroid dysfunction. Early detection of hyperthyroidism in neonates with cholestasis is crucial. neonatal cholestasis neonatal Grave’s disease neonatal hyperthyroidism Introduction Neonatal/Infantile cholestasis (NIC) is defined as an impairment in bile formation and/or flow presenting by the first year of age, typically within the first three months. This condition leads to the retention of bile and biliary substances in the liver, resulting in hepatobiliary damage[1].NIC results from diverse etiologies, including biliary atresia, infections, genetic-metabolic disorders related to hematologic, endocrine dysfunctions, etc. Congenital endocrine disorders—such as hypopituitarism, adrenal cortex hyperplasia, and hypothyroidism—are well-established causes of neonatal cholestasis. In contrast, hyperthyroidism has been less frequently associated with this condition. Here, we reported a case of neonatal cholestasis caused by Graves' disease and reviewed relevant literatures to summarize its clinical characteristics, aim to enhance recognition and diagnosis of this disease promptly and precisely. Case presentation The female neonate was delivered at 36 weeks and 5 days gestation to parents who were not consanguineous. The infant had a moderate birth weight of 2340g. The primigravida experienced a pregnancy without complications, except for a pre-existing history of Graves' disease, which was diagnosed approximately 3-4 years earlier and managed with the use of propylthiouracil (PTU). It showed stable euthyroidism, normal liver function during the whole pregnancy, and negative thyrotropin receptor antibody (TRAb) at the 12 weeks' gestation. Following the delivery, the results of her thyroid testing indicated a suppressed level of thyroid-stimulating hormone (TSH, 0.05mIU/L) and a normal level of free thyroxine (FT4). On day 1 of life (DOL), the infant was admitted to local neonatal ward due to the presence of jaundice, regurgitation, and the passage of meconium-stained amniotic fluid. Chest X-ray suggested pulmonary infection and total serum bilirubin (TB) level was 130umol/L ( normal range: 3.4-17.1umol/L ) . The thyroid function test was conducted in consideration of the patient's mother's Graves' disease. The results indicated a lowered level of TSH at 0.02 mIU/L ( normal range:0.25-7.31mIU/L ) , but a normal level of FT4 at 15.61 pmol/L ( normal range:6.44-29.6pmol/L ) . Therefore, the diagnosis of pneumonia and hyperbilirubinemia was established. Antibiotics and continuous blue light treatment were given for one week. After that, the jaundice improved with the drop of the TB level, which was 34.2 umol/L. On DOL 8. The observation of increased stool frequency, occurring at a rate of 8-12 times per day, was disregarded due to the patient's healthy appetite and the presence of yellow-colored feces. However, on DOL 15, the patient's stool exhibited a gradual lightening in coloration, and on DOL 20, jaundice reemerged. Consequently, she was referred to our liver center on DOL 26. The infant's weight on admission was 2800g.The sclera and skin were moderately yellowish. The individual exhibited a calm precordial region. The heart rate and blood pressure were within the usual range. The respiration of the individual under observation had a consistent and regular pattern.The abdomen was soft, the liver was 3 cm subcostal, with a firm consistency. The spleen was not palpable. Neurologic exam was nagetive. Common anatomic abnormalities, infections and metabolic conditions were excluded. The liver function tests verified the presence of cholestasis characterized by a low gamma-glutamyl transferase (r-GT) level, and the coagulation function remained normal. The second thyroid function test still revealed lowered TSH level and raised FT4 FT3 level (table 1). Despite treatment with ursodeoxycholic acid and fat-soluble vitamins, her cholestasis worsened, with a significant rise in bilirubin level within one week. Additionally, greasy feces and increased frequency of 6 to 12 bowl movements per day were noted during the daily ward round. On DOL 33, the jaundiced baby developed tachypnoea (respiratory rate 50–60 breaths/min) and tachycardia (heart rate 160–190 bpm) in the absence of identifiable predisposing factors. Electrocardiogram demonstrated sinus tachycardia. Echocardiography revealed mild to moderate mitral regurgitation, patent foramen ovale, increased flow rate in both branch pulmonary artery and descending aort. These findings raised a suspicion of hyperthyroidism as the underlying etiology, given it could account for all of the infant's medical issues. Eventually, the infant's elevated TRAb level (7.89IU/L, normal range:0-1.75IU/L) and persistent thyroid function abnormalities established the diagnosis of congenital Graves’ disease. Due to hepatoxicity risk, PTU and methimazole (MMI) were not given to the infant with cholestasis. Propranolol and intravenous immunoglobulins (IVIG) (2g/kg) were administered as an alternative. Following that, the infant demonstrated progressive clinical improvement. the heart and breathing rates returned to normal, the frequency of stools reduced, the level of bilirubin dropped, and the body weight gained steadily. At the 3-month follow-up evaluation, the patient demonstrated complete resolution of cholestasis with normalization of transaminases. Thyroid hormones and TRAb level kept getting better. At 4.5 months of age, the infant exhibited normal growth and development, and all test results—including those for thyroid function, TRAB level, liver function, echocardiography, and liver ultrasound—came back normal. Table 1 Infant laboratory studies *Abbreviations: TB, total bile acids; DB, direct bilirubin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; r-GT, gamma-glutamyl transferase ; TSH, thyroid-stimulating hormone; FT4, free thyroxine; FT3, free triiodothyronine; TRAb, thyrotropin receptor antibody. Reference ranges for laboratory values are shown under the row headings. Discussion Endocrine disorders may contribute to infantile cholestasis. Infantile cholestasis is linked to two endocrinopathies: hypothyroidism and hypopituitarism. Neonatal cholestasis is not commonly thought to be caused by hyperthyroidism. However, it had been reported in both the pediatric and adult population. Here we reported one case in China of neonatal cholestasis caused by Graves’ disease and reviewed 14 reported cases[2-14] of cholestasis caused by neonatal Graves' disease (Neonatal Hyperthyroidism), which were found in the Pubmed database and China National Knowledge Infrastructure database. These cases, which are presented in Table 2, led to the conclusion that hyperthyroidism has to be taken into account as a potential cause of neonatal cholestasis and liver dysfunction. Neonatal hyperthyroidism is less prevalent than congenital hypothyroidism. Most cases are transient Graves’ disease, secondary to transplacental passage of maternal thyrotropin receptor antibodies (TRAb). Among the 14 reviewed cases, 4 mothers rendered hypothyroid and treated with levothyroxine, while 9 mothers found hyperthyroidism during pregnancy or postpartum and received treatments such as radioiodine, PTU or subtotal thyroidectomy. The mother had normal thyroid function and negative TRAb during pregnancy in our case. Therefore, neither the mother's Table 2 cases Reference ranges for laboratory values are shown under the row headings. earlier medical treatment nor her thyroid health during pregnancy affect the development of newborn thyrotoxicosis. Rather, it depends on the types and titers of TSH receptor-stimulating autoantibodies, particularly in late pregnancy. Therefore, meticulous documentation of maternal thyroid disease history is essential when evaluating infants with cholestasis. Among all 15 cases, 12 were male infants and 14 were premature births. This distribution suggests that male gender and prematurity may represent significant risk factors for cholestasis in hyperthyroid infants. The hepatobiliary manifestations include cholestasis(15/15, 100%), hepatosplenomegaly（11/15, 73.3%）,coagulation dysfunction（3/15, 20%）, hyperammonemia（3/15, 20%）, liver failure（1/15, 6.7%）. All of the newborns displayed jaundice during the neonatal period, and the majority of them reached their highest conjugated bilirubin levels within DOL 6 and 4 infants had pale stool. The medians of conjunction bilirubin, ALT, AST were 119.7umol/L (range 41.1-633umol/L), 186U/L (range 10-504U/L), 600U/L (range 37-1197U/L) respectively. Beyond cholestasis, the majority of infants presented with characteristic hyperthyroidism symptoms, including tachycardia, irritability, respiratory distress, goiter, exophthalmos, pulmonary and systemic hypertension. Notably, rashes and thrombocytopenia were also frequent. However, our case manifested rapidly progressive cholestasis and atypical symptoms of hyperthyroidism, including diarrhea and slow growth. The initial improvement in TSH obscured the causal relationship between hyperthyroidism and cholestasis. It was realized that the cholestasis may be secondary to hyperthyroidism until the emergence of tachycardia and tachypnea. Consequently, in any neonate delivered to a mother with Graves' disease who exhibits cholestasis, hyperthyroidism should be prioritized as the primary etiology. Comprehensive evaluation of thyroid function and TRAb must be included. The etiology of neonatal hyperthyroidism-associated cholestasis and liver failure remains unclear. Postulated mechanisms described in the literature include potential for thyroxine-driven free radical generation or fatty deposition leading to cholestasis[15], or enlargement of the reticuloendothelial system seen in neonatal Graves’ disease may disrupt hepatic architecture and cause cholestasis[16], as well as congestive heart failure leading to cholestasis[17]. The etiology of cholestasis associated with hyperthyroidism in these instances remained unclear; nonetheless, there was a noticeable improvement in patients with commencement of antithyroid treatment. Neonatal Graves’ disease was a self-limiting illness, its duration depends on the persistence of TRAb which is gradually cleared from the neonatal circulation over time[18]. Most affected infants achieved euthyroid with undetectable antibody levels by 4 months of age. In our case and the cases reviewed, cholestasis often disappeared after 2-4 months. Jaundice in one case vanished at the age of 9 months, and transaminases returned to normal within a year. However, in the documented cases, one infant died of respiratory failure within several hours after birth[2], one infant developed Liver failure[10], and our case showed rapidly progressive cholestasis, so attention still need to be paid to monitoring liver function and follow-up. At present, the main treatment regimen is the use of antithyroid drugs, including propylthiouracil (PTU) and methimazole (MMI), among which PTU has certain hepatotoxicity and MMI is preferred in neonates, but the safe dose range of MMI and the long-term impact on neonates need further clinical research and evaluation.[19]. Severe cases have been reported to involve the use of immunoglobulins [20]and plasma exchange[21] .In most evaluated infants of neonatal cholestasis with significant hyperthyroidism, antithyroid medications including methimazole propylthiouracil and iodine were administered. However, 2 infants developed significant hepatotoxicity from MMI[5, 11]，paralleling the risk in adults[22], and Lindsey A postulated that patients with underlying cholestasis -whether secondary to hyperthyroidism or other etiologies-may be more vulnerable to MMI-induced hepatotoxicity, highlighting that additional caution in these patients is warranted . Our patient only received treatment of propranolol and IVIG, the liver function and jaundice demonstrated rapid improvement. This was a new therapeutic exploration in cases of neonatal cholestasis caused by hyperthyroidism. Conclusion We present a case of neonatal cholestasis secondary to Graves’ disease triggered by maternal Graves’ disease and review similar published cases. Our findings emphasize that neonatal Graves’ disease must be included in the differential diagnosis of cholestasis, particularly in infants whose mothers have Graves’ disease or a history of thyroid dysfunction. Early detection of hyperthyroidism in neonates with cholestasis is crucial, as untreated thyrotoxicosis may lead to life-threatening complications including hepatic failure. A meticulous maternal history, high index of suspicion, and targeted testing of maternal and neonatal thyroid function and TRAb are essential to make a prompt diagnosis. Neonatal Graves' disease should be considered when a jaundiced neonate presents thyrotoxic manifestations including tachycardia, tachypnea, irritability, feeding issues, weight gain dissatisfaction, and thrombocytopenia. Abbreviations NIC, Neonatal/Infantile cholestasis. PTU, propylthiouracil. TRAb, thyrotropin receptor antibody. TSH, thyroid-stimulating hormone. FT4, free thyroxine. DOL, day of life. TB, total serum bilirubin. r-GT, gamma-glutamyl transferase. MMI, methimazole. IVIG, intravenous immunoglobulins. DB, direct bilirubin. ALT, alanine aminotransferase. AST, aspartate aminotransferase. FT3, free triiodothyronine. Declarations Acknowledgements Not applicable. Author contributions All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work. Funding Not applicable. Data availability Data will be made available on request. Ethics approval and consent to participate This study was conducted in accordance with the Declaration of Helsinki. the Ethics Committee of Children’s Hospital of Fudan University waived the need for ethical approval for the case report. Clinical Trial Number is not applicable. Consent for publication Written informed consent for the release of identifying images or other personal or clinical details has been obtained from the participant’s parent or legal guardian. Competing interests The authors declare no competing interests. References Ranucci G, Della Corte C, Alberti D, Bondioni MP, Boroni G, Calvo PL, Cananzi M, Candusso M, Clemente MG, D'Antiga L: Diagnostic approach to neonatal and infantile cholestasis: a position paper by the SIGENP liver disease working group. Digestive and Liver Disease 2022, 54(1):40-53. Neal PR, Jansen RD, Lemons JA, Mirkin LD, Schreiner RL: Unusual manifestations of neonatal hyperthyroidism. AMERICAN JOURNAL OF PERINATOLOGY 1985, 2(3):231-235. Beroukhim RS, Moon TD, Felner EI: Neonatal thyrotoxicosis and conjugated hyperbilirubinemia. The Journal of Maternal-Fetal & Neonatal Medicine 2003, 13(6):426-428. C D, H SJ, E HL, L J: An unusual cause of neonatal coagulopathy and liver disease. Journal of Perinatology 2007, 27(5):320-322. Loomba-Albrecht LA, Bremer AA, Wong A, Philipps AF: Neonatal Cholestasis Caused by Hyperthyroidism. JPGN 2012, 54(3):433-434. Lewis KA, Lewis W, Hainline BE, Johnson N, Corkins M, Eugster EA: Neonatal Graves' disease associated with severe metabolic abnormalities. Pediatrics 2011, 128(1):e232-236. U VR, M JK, J AC, S BL: Neonatal Cholestasis Caused by Undiagnosed Maternal Graves' Disease. ACG Case Reports Journal 2015, 2(1):58-60. Khadora MM, Dubayee MA: Neonatal Graves' disease with unusual metabolic association from presentation to resolution. BMJ Case Rep 2014, 2014. Akangire G, Cuna A, Lachica C, Fischer R, Raman S, Sampath V: Neonatal Graves' Disease with Maternal Hypothyroidism. AJP Rep 2017, 7(3):e181-e184. Hasosah M, Alsaleem K, Qurashi M, Alzaben A: Neonatal Hyperthyroidism with Fulminant Liver Failure: A Case Report. J Clin Diagn Res 2017, 11(4):Sd01-sd02. Chatur N, Castro M, Tai KFY: Macular Rash, Thrombocytopenia, and Hyperbilirubinemia in a Preterm Infant. Case Rep Pediatr 2019, 2019:4076740. Tian Y-P, Luo B, Wang H, Jing H, Zhang X-F: Neonatal graves' disease complicated with cholestatic jaundice: a case report. BMC Endocr Disord 2025, 25(1):121. Xiu-jing W, Hui-min Y, Ya-ping X: Three Cases of Neonatal Hyperthyroidism. Chinese Journal of Pediatrics 2006(01):55-56. Gang D: A Case Report of Neonatal Hyperthyroidism. Journal of Clinical Pediatrics 2011, 29(02):181-182. Barra BI, Olmos R, Barrera F, Mosso L, Domínguez JM: Cholestasis secondary to hyperthyroidism in Graves' disease. Report of one case. Rev Med Chil 2020, 148(5):697-701. Haddaden M, Hanna A, Odish F, Husami S, Imam Z, Tahhan M: Cholestatic Hepatitis in Graves' Disease: A Diagnostic Challenge. ACG Case Rep J 2021, 8(1):e00526. Jr TPF: Maternally transferred thyroid disease in the infant: recognition and treatment. Adv Exp Med Biol 1991, 299:209-226. J PC, C HP: Management of neonatal endocrinopathies--best practice guidelines. Early Hum Dev 2007, 83(9):553-561. Samuels SL, Namoc SM, Bauer AJ: Neonatal Thyrotoxicosis. Clin Perinatol 2018, 45(1):31-40. Kurtoğlu S, Özdemir A: Fetal neonatal hyperthyroidism: diagnostic and therapeutic approachment. Turk Pediatri Ars 2017, 52(1):1-9. Zeng B, Yuan L, Chu J, Yang Y, Lin S: Challenges in early identification of causes and treatment of cholestasis in patients with hyperthyroidism: a case report and literature review. J Int Med Res 2020, 48(3):300060519891018. Majeed M, Babu A: Cholestasis secondary to hyperthyroidism made worse by methimazole. Am J Med Sci 2006, 332(1):51-53. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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This condition leads to the retention of bile and biliary substances in the liver, resulting in hepatobiliary damage[1].NIC results from diverse etiologies, including biliary atresia, infections, genetic-metabolic disorders related to hematologic, endocrine dysfunctions, etc. Congenital endocrine disorders—such as hypopituitarism, adrenal cortex hyperplasia, and hypothyroidism—are well-established causes of neonatal cholestasis. In contrast, hyperthyroidism has been less frequently associated with this condition. Here, we reported a case of neonatal cholestasis caused by Graves' disease and reviewed relevant literatures to summarize its clinical characteristics, aim to enhance recognition and diagnosis of this disease promptly and precisely.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eThe female neonate was delivered at 36 weeks and 5 days gestation to parents who were not consanguineous. The infant had a moderate birth weight of 2340g. The primigravida experienced a pregnancy without complications, except for a pre-existing history of \u0026nbsp;Graves\u0026apos; disease, which was diagnosed approximately 3-4 years earlier and managed with the use of propylthiouracil (PTU). It showed stable euthyroidism, normal liver function during the whole pregnancy, and negative thyrotropin receptor antibody (TRAb) at the 12 weeks\u0026apos; gestation. Following the delivery, the results of her thyroid testing indicated a suppressed level of thyroid-stimulating hormone (TSH, 0.05mIU/L) and a normal level of free thyroxine (FT4).\u003c/p\u003e\n\u003cp\u003eOn day 1 of life (DOL), the infant was admitted to local neonatal ward due to the presence of jaundice, regurgitation, and the passage of meconium-stained amniotic fluid. Chest X-ray suggested pulmonary infection and total serum bilirubin (TB) level was 130umol/L \u003cins cite=\"mailto:[email protected]\" datetime=\"2023-09-08T18:21\"\u003e(\u003c/ins\u003enormal range: 3.4-17.1umol/L\u003cins cite=\"mailto:[email protected]\" datetime=\"2023-09-08T18:21\"\u003e)\u003c/ins\u003e. The thyroid function test was conducted in consideration of the patient\u0026apos;s mother\u0026apos;s Graves\u0026apos; disease. The results indicated a lowered level of TSH at 0.02 mIU/L \u003cins cite=\"mailto:[email protected]\" datetime=\"2023-09-08T18:21\"\u003e(\u003c/ins\u003enormal range:0.25-7.31mIU/L\u003cins cite=\"mailto:[email protected]\" datetime=\"2023-09-08T18:21\"\u003e)\u003c/ins\u003e, but a normal level of FT4 at 15.61 pmol/L \u003cins cite=\"mailto:[email protected]\" datetime=\"2023-09-08T18:21\"\u003e(\u003c/ins\u003enormal range:6.44-29.6pmol/L\u003cins cite=\"mailto:[email protected]\" datetime=\"2023-09-08T18:21\"\u003e)\u003c/ins\u003e. Therefore, the diagnosis of pneumonia and hyperbilirubinemia was established. Antibiotics and continuous blue light treatment were given for one week. After that, the jaundice improved with the drop of the TB level, which was 34.2 umol/L. On DOL 8. The observation of increased stool frequency, occurring at a rate of 8-12 times per day, was disregarded due to the patient\u0026apos;s healthy appetite and the presence of yellow-colored feces.\u003c/p\u003e\n\u003cp\u003eHowever, on DOL 15, the patient\u0026apos;s stool exhibited a gradual lightening in coloration, and on DOL 20, jaundice reemerged. Consequently, she was referred to our liver center on DOL 26. The infant\u0026apos;s weight on admission was 2800g.The sclera and skin were moderately yellowish. The individual exhibited a calm precordial region. The heart rate and blood pressure were within the usual range. The respiration of the individual under observation had a consistent and regular pattern.The abdomen was soft, the liver was 3 cm subcostal, with a firm consistency. The spleen was not palpable. Neurologic exam was nagetive. Common anatomic abnormalities, infections and metabolic conditions were excluded. The liver function tests verified the presence of cholestasis characterized by a low gamma-glutamyl transferase (r-GT) level, and the coagulation function remained normal. The second thyroid function test still revealed lowered TSH level and raised FT4 FT3 level (table 1). Despite treatment with ursodeoxycholic acid and fat-soluble vitamins, her cholestasis worsened, with a significant rise in bilirubin level within one week. Additionally, greasy feces and increased frequency of 6 to 12 bowl movements per day were noted during the daily ward round. On DOL 33, the jaundiced baby developed tachypnoea (respiratory rate 50\u0026ndash;60 breaths/min) and tachycardia (heart rate 160\u0026ndash;190 bpm) in the absence of identifiable predisposing factors. Electrocardiogram demonstrated sinus tachycardia. Echocardiography revealed mild to moderate mitral regurgitation, patent foramen ovale, increased flow rate in both branch pulmonary artery and descending aort. These findings raised a suspicion of hyperthyroidism as the underlying etiology, given it could account for all of the infant\u0026apos;s medical issues. Eventually, the infant\u0026apos;s elevated TRAb level (7.89IU/L, normal range:0-1.75IU/L) and persistent thyroid function abnormalities established the diagnosis of congenital Graves\u0026rsquo; disease. Due to hepatoxicity risk, PTU and methimazole (MMI) were not given to the infant with cholestasis. Propranolol and intravenous immunoglobulins (IVIG) (2g/kg) were administered as an alternative. Following that, the infant demonstrated progressive clinical improvement. the heart and breathing rates returned to normal, the frequency of stools reduced, the level of bilirubin dropped, and the body weight gained steadily. At the 3-month follow-up evaluation, the patient demonstrated complete resolution of cholestasis with normalization of transaminases. Thyroid hormones and TRAb level kept getting better.\u003c/p\u003e\n\u003cp\u003eAt 4.5 months of age, the infant exhibited normal growth and development, and all test results\u0026mdash;including those for thyroid function, TRAB level, liver function, echocardiography, and liver ultrasound\u0026mdash;came back normal.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1 Infant laboratory studies\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cimg width=\"625\" height=\"242\" 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alt=\"表格描述已自动生成\"\u003e\u003c/p\u003e\n\u003cp\u003e*Abbreviations: TB, total bile acids; DB, direct bilirubin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; r-GT, gamma-glutamyl transferase ; TSH, thyroid-stimulating hormone; \u0026nbsp;FT4, free thyroxine; FT3, free triiodothyronine; TRAb, thyrotropin receptor antibody. Reference ranges for laboratory values are shown \u0026nbsp;under the row headings.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eEndocrine disorders may contribute to infantile cholestasis. Infantile cholestasis is linked to two endocrinopathies: hypothyroidism and hypopituitarism. Neonatal cholestasis is not commonly thought to be caused by hyperthyroidism. However, it had been reported in both the pediatric and adult population. Here we reported\u0026nbsp;one case in China of neonatal cholestasis caused by Graves\u0026rsquo; disease and reviewed 14 reported cases[2-14] of cholestasis caused by neonatal Graves\u0026apos; disease (Neonatal Hyperthyroidism), which were found in the Pubmed database and China National Knowledge Infrastructure database. These cases, which are presented in Table 2, led to the conclusion that hyperthyroidism has to be taken into account as a potential cause of neonatal cholestasis and liver dysfunction.\u003c/p\u003e\n\u003cp\u003eNeonatal hyperthyroidism is less prevalent than congenital hypothyroidism. Most cases are transient Graves\u0026rsquo; disease, secondary to transplacental passage of maternal thyrotropin receptor antibodies (TRAb).\u0026nbsp;Among the 14 reviewed cases, 4 mothers rendered hypothyroid and treated with levothyroxine, while 9 mothers found hyperthyroidism during pregnancy or postpartum and received treatments such as radioiodine, PTU or subtotal thyroidectomy. The mother had normal thyroid function and negative TRAb during pregnancy in our case. Therefore, neither the mother\u0026apos;s\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2 cases\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cimg width=\"554\" height=\"609\" 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\" alt=\"表格描述已自动生成\"\u003e\u003c/p\u003e\n\u003cp\u003eReference ranges for laboratory values are shown \u0026nbsp;under the row headings.\u003c/p\u003e\n\u003cp\u003eearlier medical treatment nor her thyroid health during pregnancy affect the development of newborn thyrotoxicosis. Rather, it depends on the types and titers of TSH receptor-stimulating autoantibodies, particularly in late pregnancy. Therefore, meticulous documentation of maternal thyroid disease history is essential when evaluating infants with cholestasis.\u003c/p\u003e\n\u003cp\u003eAmong all 15 cases, 12 were male infants and 14 were premature births. This distribution suggests that male gender and prematurity may represent significant risk factors for cholestasis in hyperthyroid infants. The hepatobiliary manifestations include cholestasis(15/15, 100%), hepatosplenomegaly（11/15, 73.3%）,coagulation dysfunction（3/15, 20%）, hyperammonemia（3/15, 20%）, liver failure（1/15, 6.7%）. All\u003cins cite=\"mailto:[email protected]\" datetime=\"2023-09-07T19:01\"\u003e\u0026nbsp;\u003c/ins\u003eof the newborns displayed jaundice during the neonatal period, and the majority of them reached their highest conjugated bilirubin levels within DOL 6 and 4 infants had pale stool. The medians of conjunction bilirubin, ALT, AST were 119.7umol/L (range 41.1-633umol/L), 186U/L (range 10-504U/L), 600U/L (range 37-1197U/L) respectively. Beyond cholestasis, the majority of infants presented with characteristic hyperthyroidism symptoms, including tachycardia, irritability, respiratory distress, goiter, exophthalmos, pulmonary and systemic hypertension. Notably, rashes and thrombocytopenia were also frequent. However, our case manifested rapidly progressive cholestasis and atypical symptoms of hyperthyroidism, including diarrhea and slow growth. The initial improvement in TSH obscured the causal relationship between hyperthyroidism and cholestasis. It was realized that the cholestasis may be secondary to hyperthyroidism until the emergence of tachycardia and tachypnea. Consequently, in any neonate delivered to a mother with Graves\u0026apos; disease who exhibits cholestasis, hyperthyroidism should be prioritized as the primary etiology. Comprehensive evaluation of thyroid function and TRAb must be included.\u003c/p\u003e\n\u003cp\u003eThe etiology of neonatal hyperthyroidism-associated cholestasis and liver failure remains unclear. Postulated mechanisms described in the literature include potential for thyroxine-driven free radical generation or fatty deposition leading to cholestasis[15], or enlargement of the reticuloendothelial system seen in neonatal Graves\u0026rsquo; disease may disrupt hepatic architecture and cause cholestasis[16], as well as congestive heart failure leading to cholestasis[17].\u0026nbsp;The etiology of cholestasis associated with hyperthyroidism in these instances remained unclear; nonetheless, there was a noticeable improvement in patients with commencement of antithyroid treatment.\u003c/p\u003e\n\u003cp\u003eNeonatal Graves\u0026rsquo; disease was a self-limiting illness, its duration depends on the persistence of \u0026nbsp; TRAb which is gradually cleared from the neonatal circulation over time[18].\u0026nbsp;Most affected infants achieved euthyroid with undetectable antibody levels by 4 months of age. In our case and the cases reviewed, cholestasis often disappeared after 2-4 months. Jaundice in one case vanished at the age of \u0026nbsp;9 months, and transaminases returned to normal within a year. \u0026nbsp;However, in the documented cases, one infant died of respiratory failure within several \u0026nbsp;hours after birth[2], one infant developed Liver failure[10], and our case showed rapidly progressive cholestasis, so attention still need to be paid to monitoring liver function and follow-up. At present, the main treatment regimen is the use of antithyroid drugs, including propylthiouracil (PTU) and methimazole (MMI), among which PTU has certain hepatotoxicity and MMI is preferred in neonates, but the safe dose range of MMI and the long-term impact on neonates need further clinical research and evaluation.[19]. Severe cases have been reported to involve the use of immunoglobulins\u0026nbsp;[20]and plasma exchange[21]\u0026nbsp;.In most evaluated infants of neonatal cholestasis with significant hyperthyroidism, antithyroid medications including methimazole propylthiouracil and iodine were administered. However, 2 infants developed significant hepatotoxicity\u0026nbsp;from MMI[5, 11]，paralleling the risk in adults[22], and Lindsey A postulated that patients with underlying cholestasis -whether secondary to hyperthyroidism or other etiologies-may be more vulnerable to MMI-induced hepatotoxicity, highlighting that additional caution in these patients is warranted\u003cins cite=\"mailto:jerry\" datetime=\"2025-06-24T20:25\"\u003e.\u003c/ins\u003e Our patient only received treatment of propranolol and IVIG, the liver function and jaundice demonstrated rapid improvement. This was a new therapeutic exploration in cases of neonatal cholestasis caused by hyperthyroidism.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eWe present a case of neonatal cholestasis secondary to Graves\u0026rsquo; disease triggered by maternal Graves\u0026rsquo; disease and review similar published cases. Our findings emphasize that neonatal Graves\u0026rsquo; disease must be included in the differential diagnosis of cholestasis, particularly in infants whose mothers have Graves\u0026rsquo; disease or a history of thyroid dysfunction. Early detection of hyperthyroidism in neonates with cholestasis is crucial, as untreated thyrotoxicosis may lead to life-threatening complications including hepatic failure. A meticulous maternal history, high index of suspicion, and targeted testing of maternal and neonatal thyroid function and TRAb are essential to make a prompt diagnosis. Neonatal Graves' disease should be considered when a jaundiced neonate presents thyrotoxic manifestations including tachycardia, tachypnea, irritability, feeding issues, weight gain dissatisfaction, and thrombocytopenia.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eNIC, Neonatal/Infantile cholestasis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePTU, propylthiouracil.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTRAb, thyrotropin receptor antibody.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTSH, thyroid-stimulating hormone.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFT4, free thyroxine.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDOL, day of life.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTB, total serum bilirubin.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003er-GT,\u0026nbsp;gamma-glutamyl transferase.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMMI, methimazole.\u003c/p\u003e\n\u003cp\u003eIVIG, intravenous immunoglobulins.\u003c/p\u003e\n\u003cp\u003eDB, direct bilirubin.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eALT, alanine aminotransferase.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAST, aspartate aminotransferase.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFT3, free triiodothyronine.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData will be made available on request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the Declaration of Helsinki. the Ethics Committee of Children’s Hospital of Fudan University waived the need for ethical approval for the case report. Clinical Trial Number is not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for the release of identifying images or other personal or clinical details has been obtained from the participant’s parent or legal guardian.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eRanucci G, Della Corte C, Alberti D, Bondioni MP, Boroni G, Calvo PL, Cananzi M, Candusso M, Clemente MG, D\u0026apos;Antiga L: Diagnostic approach to neonatal and infantile cholestasis: a position paper by the SIGENP liver disease working group. \u003cem\u003eDigestive and Liver Disease\u0026nbsp;\u003c/em\u003e2022, 54(1):40-53.\u003c/li\u003e\n \u003cli\u003eNeal PR, Jansen RD, Lemons JA, Mirkin LD, Schreiner RL: Unusual manifestations of neonatal hyperthyroidism. \u003cem\u003eAMERICAN JOURNAL OF PERINATOLOGY\u0026nbsp;\u003c/em\u003e1985, 2(3):231-235.\u003c/li\u003e\n \u003cli\u003eBeroukhim RS, Moon TD, Felner EI: Neonatal thyrotoxicosis and conjugated hyperbilirubinemia. \u003cem\u003eThe Journal of Maternal-Fetal \u0026amp; Neonatal Medicine\u0026nbsp;\u003c/em\u003e2003, 13(6):426-428.\u003c/li\u003e\n \u003cli\u003eC D, H SJ, E HL, L J: An unusual cause of neonatal coagulopathy and liver disease. \u003cem\u003eJournal of Perinatology\u0026nbsp;\u003c/em\u003e2007, 27(5):320-322.\u003c/li\u003e\n \u003cli\u003eLoomba-Albrecht LA, Bremer AA, Wong A, Philipps AF: Neonatal Cholestasis Caused by Hyperthyroidism. \u003cem\u003eJPGN\u0026nbsp;\u003c/em\u003e2012, 54(3):433-434.\u003c/li\u003e\n \u003cli\u003eLewis KA, Lewis W, Hainline BE, Johnson N, Corkins M, Eugster EA: Neonatal Graves\u0026apos; disease associated with severe metabolic abnormalities. \u003cem\u003ePediatrics\u0026nbsp;\u003c/em\u003e2011, 128(1):e232-236.\u003c/li\u003e\n \u003cli\u003eU VR, M JK, J AC, S BL: Neonatal Cholestasis Caused by Undiagnosed Maternal Graves\u0026apos; Disease. \u003cem\u003eACG Case Reports Journal\u0026nbsp;\u003c/em\u003e2015, 2(1):58-60.\u003c/li\u003e\n \u003cli\u003eKhadora MM, Dubayee MA: Neonatal Graves\u0026apos; disease with unusual metabolic association from presentation to resolution. \u003cem\u003eBMJ Case Rep\u0026nbsp;\u003c/em\u003e2014, 2014.\u003c/li\u003e\n \u003cli\u003eAkangire G, Cuna A, Lachica C, Fischer R, Raman S, Sampath V: Neonatal Graves\u0026apos; Disease with Maternal Hypothyroidism. \u003cem\u003eAJP Rep\u0026nbsp;\u003c/em\u003e2017, 7(3):e181-e184.\u003c/li\u003e\n \u003cli\u003eHasosah M, Alsaleem K, Qurashi M, Alzaben A: Neonatal Hyperthyroidism with Fulminant Liver Failure: A Case Report. \u003cem\u003eJ Clin Diagn Res\u0026nbsp;\u003c/em\u003e2017, 11(4):Sd01-sd02.\u003c/li\u003e\n \u003cli\u003eChatur N, Castro M, Tai KFY: Macular Rash, Thrombocytopenia, and Hyperbilirubinemia in a Preterm Infant. \u003cem\u003eCase Rep Pediatr\u0026nbsp;\u003c/em\u003e2019, 2019:4076740.\u003c/li\u003e\n \u003cli\u003eTian Y-P, Luo B, Wang H, Jing H, Zhang X-F: Neonatal graves\u0026apos; disease complicated with cholestatic jaundice: a case report. \u003cem\u003eBMC Endocr Disord\u0026nbsp;\u003c/em\u003e2025, 25(1):121.\u003c/li\u003e\n \u003cli\u003eXiu-jing W, Hui-min Y, Ya-ping X: Three Cases of Neonatal Hyperthyroidism. \u003cem\u003eChinese Journal of Pediatrics\u0026nbsp;\u003c/em\u003e2006(01):55-56.\u003c/li\u003e\n \u003cli\u003eGang D: A Case Report of Neonatal Hyperthyroidism. \u003cem\u003eJournal of Clinical Pediatrics\u0026nbsp;\u003c/em\u003e2011, 29(02):181-182.\u003c/li\u003e\n \u003cli\u003eBarra BI, Olmos R, Barrera F, Mosso L, Dom\u0026iacute;nguez JM: Cholestasis secondary to hyperthyroidism in Graves\u0026apos; disease. Report of one case. \u003cem\u003eRev Med Chil\u0026nbsp;\u003c/em\u003e2020, 148(5):697-701.\u003c/li\u003e\n \u003cli\u003eHaddaden M, Hanna A, Odish F, Husami S, Imam Z, Tahhan M: Cholestatic Hepatitis in Graves\u0026apos; Disease: A Diagnostic Challenge. \u003cem\u003eACG Case Rep J\u0026nbsp;\u003c/em\u003e2021, 8(1):e00526.\u003c/li\u003e\n \u003cli\u003eJr TPF: Maternally transferred thyroid disease in the infant: recognition and treatment. \u003cem\u003eAdv Exp Med Biol\u0026nbsp;\u003c/em\u003e1991, 299:209-226.\u003c/li\u003e\n \u003cli\u003eJ PC, C HP: Management of neonatal endocrinopathies--best practice guidelines. \u003cem\u003eEarly Hum Dev\u0026nbsp;\u003c/em\u003e2007, 83(9):553-561.\u003c/li\u003e\n \u003cli\u003eSamuels SL, Namoc SM, Bauer AJ: Neonatal Thyrotoxicosis. \u003cem\u003eClin Perinatol\u0026nbsp;\u003c/em\u003e2018, 45(1):31-40.\u003c/li\u003e\n \u003cli\u003eKurtoğlu S, \u0026Ouml;zdemir A: Fetal neonatal hyperthyroidism: diagnostic and therapeutic approachment. \u003cem\u003eTurk Pediatri Ars\u0026nbsp;\u003c/em\u003e2017, 52(1):1-9.\u003c/li\u003e\n \u003cli\u003eZeng B, Yuan L, Chu J, Yang Y, Lin S: Challenges in early identification of causes and treatment of cholestasis in patients with hyperthyroidism: a case report and literature review. \u003cem\u003eJ Int Med Res\u0026nbsp;\u003c/em\u003e2020, 48(3):300060519891018.\u003c/li\u003e\n \u003cli\u003eMajeed M, Babu A: Cholestasis secondary to hyperthyroidism made worse by methimazole. \u003cem\u003eAm J Med Sci\u0026nbsp;\u003c/em\u003e2006, 332(1):51-53.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"neonatal cholestasis, neonatal Grave’s disease, neonatal hyperthyroidism","lastPublishedDoi":"10.21203/rs.3.rs-7000759/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7000759/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eObjective\u003c/b\u003e\u003c/p\u003e\u003cp\u003eNeonatal/Infantile cholestasis (NIC) is defined as an impairment in bile formation and/or flow presenting by the first year of age, typically within the first three months. Hyperthyroidism has been less frequently associated with this condition. Here, we reported a case of neonatal cholestasis caused by Graves' disease and reviewed relevant literatures to summarize its clinical characteristics, aim to enhance recognition and diagnosis of this disease promptly and precisely.\u003c/p\u003e\u003cp\u003e\u003cb\u003eCase presentation\u003c/b\u003e\u003c/p\u003e\u003cp\u003eA 28-day-old female infant was admitted to our center, presented with jaundice, diarrhea, poor weight gain, and tachycardia. laboratory examinations showed cholestasis, hyperthyroidism and positive thyroid receptor antibody, confirming the diagnosis of neonatal Grave\u0026rsquo;s disease. After treatment with Propranolol and intravenous immunoglobulins (IVIG), the jaundice subsided and thyroid function returned to normal.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e\u003c/p\u003e\u003cp\u003eneonatal Graves\u0026rsquo; disease must be included in the differential diagnosis of cholestasis, particularly in infants whose mothers have Graves\u0026rsquo; disease or a history of thyroid dysfunction. Early detection of hyperthyroidism in neonates with cholestasis is crucial.\u003c/p\u003e","manuscriptTitle":"Neonatal cholestasis caused by Graves’ disease：a case report and literature review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-14 07:24:04","doi":"10.21203/rs.3.rs-7000759/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0dba50df-cf0f-4eaf-ae3c-e2de7d13bc66","owner":[],"postedDate":"July 14th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-21T11:15:38+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-14 07:24:04","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7000759","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7000759","identity":"rs-7000759","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}