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A rare case of large pericardial effusion in a child with severe primary hypothyroidism
Progress in Pediatric Cardiology xxx (xxxx) xxxx
Contents lists available at ScienceDirect
Progress in Pediatric Cardiology journal homepage: www.elsevier.com/locate/ppedcard
A rare case of large pericardial effusion in a child with severe primary hypothyroidism Arun Bableshwar, Sagar Mali
⁎
SDM Narayana Heart Centre, Manjushree building, 5th Floor, SDM College of Medical Sciences and Hospital Campus, Sattur, Dharwad 580009, Karnataka, India
ARTICLE INFO
ABSTRACT
Keywords: Pediatric pericardial effusion Primary hypothyroidism Pericardiocentesis Screening programs
Thyroid disorders are a common clinical entity and hypothyroidism is the most common thyroid disorder encountered in the Indian population. Its diagnosis is simple but often remains undiagnosed or misdiagnosed because of the sub-clinical course of disease. It was a familiar scenario in the past when diagnosis of hypothyroidism was confirmed after admission of patient due to complications secondary to hypothyroidism such as myxedema coma, infertility, impaired fertility, goiter, easy miscarriage, birth defects, mental retardation, dyslipidemia, psychological problems, cardiomyopathy, heart failure, depression. Usually, such case reports were reported in adult patients. We are reporting a case of large pericardial effusion in a child with severe primary hypothyroidism.
1. Introduction In India, it has been estimated that 42 million people suffer from thyroid disorders. Among these disorders, hypothyroidism is a common endocrine disorder seen in the Indian population, with prevalence of around 11%, i.e. it affects nearly 1 in every 10 adults [1]. Studies by Wu T et al. and Lazar L et al., which involved large study populations, showed prevalence of mild hypothyroidism in children ranges from 1.7% to 2.9% [2,3]. The incidence of hypothyroid pericardial effusion varies from 3% (in early mild stage) to 80% (in advanced disease) [4].We are reporting a case of large pericardial effusion in a child with severe primary hypothyroidism. 2. Text 2.1. Case presentation A twelve year old girl presented to the cardiac out-patient department with gradually progressive dyspnoea on exertion for the past six months. It was increased in the last two weeks (progressed to NYHA class 3). She also gave history of abdominal distention, ab-
⁎
dominal pain, and constipation of two weeks duration. She complained of lethargy, easy fatiguability, weight gain, cold intolerance, anorexia and dry skin since one year. She did not give any history of fever or cough. On examination, she was conscious, co-operative and well oriented to time, place and person. Her vital data showed pulse rate-104 bpm, blood pressure-86/51 mmHg, respiratory rate-22/min, SPO2-96% at room air and she was afebrile. General physical examination of patient showed periorbital and facial puffiness and pedal edema. Her thyroid gland was not enlarged and could not be felt on palpation. The rest of the physical examination was inconclusive. On investigation, ECG showed sinus tachycardia and low voltage complexes (Image 1). Echocardiography showed large circumferential pericardial effusion without tamponade or PAH (pulmonary artery hypertension) with normal left ventricular function. Her chest X-ray showed enlarged cardiac silhouette and clear lungs (Image 2). She was admitted in the cardiac intensive care unit for emergency pericardiocentesis. Her lab values are summarized in Table 1 below,
Corresponding author. E-mail addresses: [email protected] (A. Bableshwar), [email protected] (S. Mali).
https://doi.org/10.1016/j.ppedcard.2019.101186 Received 21 September 2019; Received in revised form 4 December 2019; Accepted 4 December 2019 1058-9813/ © 2019 Elsevier B.V. All rights reserved.
Please cite this article as: Arun Bableshwar and Sagar Mali, Progress in Pediatric Cardiology, https://doi.org/10.1016/j.ppedcard.2019.101186
Progress in Pediatric Cardiology xxx (xxxx) xxxx
A. Bableshwar and S. Mali
Table 1
She underwent emergency USG guided pericardiocentesis through subxiphoid approach. A total of 150 mL of light yellow colored fluid was aspirated and sent for analysis. Cytological analysis, biochemistry and microbiological tests on pericardial fluid were unremarkable. Primary hypothyroidism was confirmed as the cause of large pericardial effusion. Patient was started on Levothyroxine 150 μg/day and discharged after 48 h of observation in a stable condition.
Showing lab investigation report. Parameter Blood investigation Hemoglobin Total count Renal function tests Blood urea Serum creatinine Liver function tests Total protein Albumin AST ALT Alkaline phosphatase GGT Viral markers HIV HCV HBsAg Pericardial fluid analysis Microscopy Biochemistry Protein Sugar Cytology Cell count Differential count Thyroid function tests Serum T3 Serum T4 TSH Hematology Prothrombin time Partial thromboplastin time INR
Result
Ref. range
11.9 g/dL 11,100 cells/mm3
12–16 4000–12,000
25.6 mg/dL 0.58 mg/dL
15–45 0.5–1.2
9.4 g/dL 4.9 g/dL 34 U/L 22 U/L 57 U/L 17 U/L
3.5–5 15–59 13–72 38–126 12–73
2.2. Discussion The usual presentation of hypothyroidism includes the following signs and symptoms; lethargy, cold intolerance, constipation, weight gain, dry skin, hair loss, bradycardia, psychomotor retardation. In extreme cases with long standing hypothyroidism, patient can present with a dangerous complication i.e. myxedema coma (coma with extreme hypothermia, respiratory depression with hypercapnia, areflexia and bradycardia) [5]. It can independently affect and have long lasting effects on the cardiovascular system. It can increase morbidity and mortality by enhancing risk factors like hypertension and hyperlipidemia [6,7]. It is also found that cases of sub-clinical hypothyroidism with moderate severity in younger population are at higher risk of developing stroke and heart failure [8]. The mechanism of pericardial effusion secondary to hypothyroidism is due to increased permeability of epicardial vessels causing extravasation of albumin in the pericardial sac and decreased lymphatic drainage of albumin, which results in fluid accumulation in the pericardial space [9]. The complexes formed between hyaluronic acid and albumin is responsible for slow lymphatic drainage of albumin. According to recent studies, low levels of nitric oxide is responsible for increased permeability of capillaries thus causing albumin extravasation and endothelial dysfunction [10]. The rate of fluid accumulation determines the clinical picture and its management. Even a small amount of fluid that gets accumulated rapidly in the pericardial space can cause cardiac tamponade and requires emergency pericardiocentesis. A large retrospective cohort study by Bolin E H et al., analyzed 9,902 non-postoperative pediatric pericardial effusion (PCE) cases and found that maximum PCE cases were due to idiopathic cause (36%), followed by neoplasms (24%), pneumonia (20%), autoimmune/inflammatory disease (19%), bacterial infection (13%), viral infection
Non-reactive Non-reactive Negative Gram stain- occasional pus cells, no organisms seen ZN stain- negative for acid fast bacilli 6.4 mg% 88 mg%
15–45 70–110
Nucleated cells- 95 cells/cmm RBC's- 50 cells/cmm Mesothelial cells 80% Lymphocyte 10% Neutrophil 10% 0.46 nmol/L 20.37 nmol/L > 100 mcIU/mL
1.2–3.1 66–181 0.7–6.4
14.5 s 37.9 s
Control 12.4 s Control 31 s
1.18
Her echocardiography showed large circumferential pericardial effusion with no evidence of tamponade or pulmonary artery hypertension (Image 3).
Image 1. ECG showing low voltage complexes. 2
Progress in Pediatric Cardiology xxx (xxxx) xxxx
A. Bableshwar and S. Mali
view of large pericardial effusion, hypotension, and impending tamponade. Patient was diagnosed as a case of primary hypothyroidism and started on Levothyroxine 150 μg/day. She was discharged with no pericardial effusion and showed no recurrence of effusion during her follow-up visits to the cardiac outpatient department. 2.3. Conclusion Ideally, every newborn at birth and student in schools and colleges should be screened for hypothyroidism on a regular basis, and more emphasis should be given on the screening of female students and on those with a family history of thyroid disorder. Some steps recommended below can help to improve the current situation and help align India's health priorities with current health care needs.
• To initiate a national neonatal screening program which will include Image 2. Chest X-ray showing enlarged cardiac silhouette and clear lungs.
(8%), renal (6%), hypothyroidism (2%) [11]. Hypothyroidism in newborn and young infants could be due to thyroid dysgenesis or dyshormonogenesis [12]. Severe hypothyroidism in older children and adolescents is usually caused by autoimmune thyroiditis (e.g. Hashimoto's thyroiditis), iodine deficiency, genetic syndromes (e.g. Down syndrome, Turner syndrome), and other autoimmune diseases (e.g. celiac disease, type 1 diabetes mellitus), medications (e.g. IFN-alpha, antiepileptics, lithium, sertraline, ionizing radiation) [13,14]. Most cases of pericardial effusion caused by hypothyroidism needs achieving euthyroid state. The effusion usually resolves over several months. Anti-inflammatory medication and colchicine is advised only in definitive acute pericarditis cases [15]. In our case, patient underwent emergency pericardiocentesis in
• •
screening of congenital hypothyroidism as well as strengthening of Rashtriya Bal Swasthya Karyakram (RBSK) child health screening and early intervention services to improve intersectoral coordination between pediatrician, endocrinologist, and public health professionals to streamline screening for thyroid disorders through RBSK. To initiate a national program for screening and treating hypothyroidism in pregnancy and follow national guidelines for screening of hypothyroidism released in 2014. To continue the national iodine deficiency disorders control program (started since 1987)
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Image 3. Echocardiography pictures showing large pericardial effusion.
3
Progress in Pediatric Cardiology xxx (xxxx) xxxx
A. Bableshwar and S. Mali
Acknowledgement [7]
I would like to thank Dr. Vivekanand S Gajapati, Head of Department, Cardiology for his expert advice and encouragement. I would also like to thank Dr. Kirti L for her support.
[8] [9]
References
[10]
[1] Bagcchi S. Hypothyroidism in India: more to be done. Lancet Diabetes Endocrinol 2014;2:778. [2] Wu T, Flowers JW, Tudiver F, Wilson JL, Punyasavatsut N. Subclinical thyroid disorders and cognitive performance among adolescents in the United States. BMC Pediatr 2006;6:12. [3] Lazar L, Frumkin RB, Battat E, Lebenthal Y, Phillip M, Meyerovitch J. Natural history of thyroid function tests over 5 years in a large pediatric cohort. J Clin Endocrinol Metab 2009;94:1678–82. [4] Purkait R, Prasad A, Bhadra R, Basu A. Massive pericardial effusion as the only manifestation of primary hypothyroidism. J Cardiovasc Dis Res 2013;4:248–50. [5] Ravinder Reddy K, Mudgalkar N, Sivarama Prasad L. A rare case of hypothyroidism presenting as massive pericardial effusion with cardiac tamponade. Perspect Med Res 2015;3(2):27–8. [6] Laulund AS, Nybo M, Brix TH, Abrahamsen B, Jørgensen HL, Hegedüs L. Duration of thyroid dysfunction correlates with all-cause mortality. The OPENTHYRO Register
[11]
[12] [13] [14] [15]
4
Cohort. PLoS One 2014;9(10):e110437https://doi.org/10.1371/journal.pone. 0110437. Dörr HV. Cardiovascular morbidity and mortality in thyroid dysfunction. Minerva Endocrinol 2005;30:199–216. Chaker L, Bianco AC, Jonklaas J, Peeters RP. Hypothyroidism. Lancet 2017;390:1550–62. Motabar A, Anousheh R, Shaker R, Pai RG. A rare case of amiodaroneinduced hypothyroidism presenting with cardiac tamponade. Int J Angiol 2011;20:177–80. Sondhi S, Bhardwaj R, Kandoria A, Ganju N, Mahajan K, et al. Massive pericardial effusion–rare and only presentation of hypothyrodism – myxedematous heart. J Cardiovasc Dis Diagn 2017;5:286. https://doi.org/10.4172/2329-9517.1000286. Bolin EH, Tang X, Lang SM, Daily JA, Collins RT. Characteristics of non-postoperative pediatric pericardial effusion: a multicenter retrospective cohort study from the Pediatric Health Information System (PHIS). Pediatr Cardiol 2018;39:347–53. https://doi.org/10.1007/s00246-017-1762-y. Marzuillo P, Grandone A, Perrotta S, et al. Very early onset of autoimmune thyroiditis in a toddler with severe hypothyroidism presentation: a case report. Ital J Pediatr 2016;42:61. Vigone MC, Capalbo D, Weber G, Salerno M. Mild hypothyroidism in childhood: who, when, and how should be treated? J Endocr Soc 2018;2:1024–39. Martinez-Soto T, Deal C, Stephure D, Trussell R, Boutin C, Djemli A, et al. Pericardial effusion in severe hypothyroidism in children. J Pediatr Endocrinol Metab 2010;23:1165–8. Chahine J, Ala CK, Gentry JL, et al. Pericardial diseases in patients with hypothyroidism. Heart 2019;105:1027–33.
Contents lists available at ScienceDirect
Progress in Pediatric Cardiology journal homepage: www.elsevier.com/locate/ppedcard
A rare case of large pericardial effusion in a child with severe primary hypothyroidism Arun Bableshwar, Sagar Mali
⁎
SDM Narayana Heart Centre, Manjushree building, 5th Floor, SDM College of Medical Sciences and Hospital Campus, Sattur, Dharwad 580009, Karnataka, India
ARTICLE INFO
ABSTRACT
Keywords: Pediatric pericardial effusion Primary hypothyroidism Pericardiocentesis Screening programs
Thyroid disorders are a common clinical entity and hypothyroidism is the most common thyroid disorder encountered in the Indian population. Its diagnosis is simple but often remains undiagnosed or misdiagnosed because of the sub-clinical course of disease. It was a familiar scenario in the past when diagnosis of hypothyroidism was confirmed after admission of patient due to complications secondary to hypothyroidism such as myxedema coma, infertility, impaired fertility, goiter, easy miscarriage, birth defects, mental retardation, dyslipidemia, psychological problems, cardiomyopathy, heart failure, depression. Usually, such case reports were reported in adult patients. We are reporting a case of large pericardial effusion in a child with severe primary hypothyroidism.
1. Introduction In India, it has been estimated that 42 million people suffer from thyroid disorders. Among these disorders, hypothyroidism is a common endocrine disorder seen in the Indian population, with prevalence of around 11%, i.e. it affects nearly 1 in every 10 adults [1]. Studies by Wu T et al. and Lazar L et al., which involved large study populations, showed prevalence of mild hypothyroidism in children ranges from 1.7% to 2.9% [2,3]. The incidence of hypothyroid pericardial effusion varies from 3% (in early mild stage) to 80% (in advanced disease) [4].We are reporting a case of large pericardial effusion in a child with severe primary hypothyroidism. 2. Text 2.1. Case presentation A twelve year old girl presented to the cardiac out-patient department with gradually progressive dyspnoea on exertion for the past six months. It was increased in the last two weeks (progressed to NYHA class 3). She also gave history of abdominal distention, ab-
⁎
dominal pain, and constipation of two weeks duration. She complained of lethargy, easy fatiguability, weight gain, cold intolerance, anorexia and dry skin since one year. She did not give any history of fever or cough. On examination, she was conscious, co-operative and well oriented to time, place and person. Her vital data showed pulse rate-104 bpm, blood pressure-86/51 mmHg, respiratory rate-22/min, SPO2-96% at room air and she was afebrile. General physical examination of patient showed periorbital and facial puffiness and pedal edema. Her thyroid gland was not enlarged and could not be felt on palpation. The rest of the physical examination was inconclusive. On investigation, ECG showed sinus tachycardia and low voltage complexes (Image 1). Echocardiography showed large circumferential pericardial effusion without tamponade or PAH (pulmonary artery hypertension) with normal left ventricular function. Her chest X-ray showed enlarged cardiac silhouette and clear lungs (Image 2). She was admitted in the cardiac intensive care unit for emergency pericardiocentesis. Her lab values are summarized in Table 1 below,
Corresponding author. E-mail addresses: [email protected] (A. Bableshwar), [email protected] (S. Mali).
https://doi.org/10.1016/j.ppedcard.2019.101186 Received 21 September 2019; Received in revised form 4 December 2019; Accepted 4 December 2019 1058-9813/ © 2019 Elsevier B.V. All rights reserved.
Please cite this article as: Arun Bableshwar and Sagar Mali, Progress in Pediatric Cardiology, https://doi.org/10.1016/j.ppedcard.2019.101186
Progress in Pediatric Cardiology xxx (xxxx) xxxx
A. Bableshwar and S. Mali
Table 1
She underwent emergency USG guided pericardiocentesis through subxiphoid approach. A total of 150 mL of light yellow colored fluid was aspirated and sent for analysis. Cytological analysis, biochemistry and microbiological tests on pericardial fluid were unremarkable. Primary hypothyroidism was confirmed as the cause of large pericardial effusion. Patient was started on Levothyroxine 150 μg/day and discharged after 48 h of observation in a stable condition.
Showing lab investigation report. Parameter Blood investigation Hemoglobin Total count Renal function tests Blood urea Serum creatinine Liver function tests Total protein Albumin AST ALT Alkaline phosphatase GGT Viral markers HIV HCV HBsAg Pericardial fluid analysis Microscopy Biochemistry Protein Sugar Cytology Cell count Differential count Thyroid function tests Serum T3 Serum T4 TSH Hematology Prothrombin time Partial thromboplastin time INR
Result
Ref. range
11.9 g/dL 11,100 cells/mm3
12–16 4000–12,000
25.6 mg/dL 0.58 mg/dL
15–45 0.5–1.2
9.4 g/dL 4.9 g/dL 34 U/L 22 U/L 57 U/L 17 U/L
3.5–5 15–59 13–72 38–126 12–73
2.2. Discussion The usual presentation of hypothyroidism includes the following signs and symptoms; lethargy, cold intolerance, constipation, weight gain, dry skin, hair loss, bradycardia, psychomotor retardation. In extreme cases with long standing hypothyroidism, patient can present with a dangerous complication i.e. myxedema coma (coma with extreme hypothermia, respiratory depression with hypercapnia, areflexia and bradycardia) [5]. It can independently affect and have long lasting effects on the cardiovascular system. It can increase morbidity and mortality by enhancing risk factors like hypertension and hyperlipidemia [6,7]. It is also found that cases of sub-clinical hypothyroidism with moderate severity in younger population are at higher risk of developing stroke and heart failure [8]. The mechanism of pericardial effusion secondary to hypothyroidism is due to increased permeability of epicardial vessels causing extravasation of albumin in the pericardial sac and decreased lymphatic drainage of albumin, which results in fluid accumulation in the pericardial space [9]. The complexes formed between hyaluronic acid and albumin is responsible for slow lymphatic drainage of albumin. According to recent studies, low levels of nitric oxide is responsible for increased permeability of capillaries thus causing albumin extravasation and endothelial dysfunction [10]. The rate of fluid accumulation determines the clinical picture and its management. Even a small amount of fluid that gets accumulated rapidly in the pericardial space can cause cardiac tamponade and requires emergency pericardiocentesis. A large retrospective cohort study by Bolin E H et al., analyzed 9,902 non-postoperative pediatric pericardial effusion (PCE) cases and found that maximum PCE cases were due to idiopathic cause (36%), followed by neoplasms (24%), pneumonia (20%), autoimmune/inflammatory disease (19%), bacterial infection (13%), viral infection
Non-reactive Non-reactive Negative Gram stain- occasional pus cells, no organisms seen ZN stain- negative for acid fast bacilli 6.4 mg% 88 mg%
15–45 70–110
Nucleated cells- 95 cells/cmm RBC's- 50 cells/cmm Mesothelial cells 80% Lymphocyte 10% Neutrophil 10% 0.46 nmol/L 20.37 nmol/L > 100 mcIU/mL
1.2–3.1 66–181 0.7–6.4
14.5 s 37.9 s
Control 12.4 s Control 31 s
1.18
Her echocardiography showed large circumferential pericardial effusion with no evidence of tamponade or pulmonary artery hypertension (Image 3).
Image 1. ECG showing low voltage complexes. 2
Progress in Pediatric Cardiology xxx (xxxx) xxxx
A. Bableshwar and S. Mali
view of large pericardial effusion, hypotension, and impending tamponade. Patient was diagnosed as a case of primary hypothyroidism and started on Levothyroxine 150 μg/day. She was discharged with no pericardial effusion and showed no recurrence of effusion during her follow-up visits to the cardiac outpatient department. 2.3. Conclusion Ideally, every newborn at birth and student in schools and colleges should be screened for hypothyroidism on a regular basis, and more emphasis should be given on the screening of female students and on those with a family history of thyroid disorder. Some steps recommended below can help to improve the current situation and help align India's health priorities with current health care needs.
• To initiate a national neonatal screening program which will include Image 2. Chest X-ray showing enlarged cardiac silhouette and clear lungs.
(8%), renal (6%), hypothyroidism (2%) [11]. Hypothyroidism in newborn and young infants could be due to thyroid dysgenesis or dyshormonogenesis [12]. Severe hypothyroidism in older children and adolescents is usually caused by autoimmune thyroiditis (e.g. Hashimoto's thyroiditis), iodine deficiency, genetic syndromes (e.g. Down syndrome, Turner syndrome), and other autoimmune diseases (e.g. celiac disease, type 1 diabetes mellitus), medications (e.g. IFN-alpha, antiepileptics, lithium, sertraline, ionizing radiation) [13,14]. Most cases of pericardial effusion caused by hypothyroidism needs achieving euthyroid state. The effusion usually resolves over several months. Anti-inflammatory medication and colchicine is advised only in definitive acute pericarditis cases [15]. In our case, patient underwent emergency pericardiocentesis in
• •
screening of congenital hypothyroidism as well as strengthening of Rashtriya Bal Swasthya Karyakram (RBSK) child health screening and early intervention services to improve intersectoral coordination between pediatrician, endocrinologist, and public health professionals to streamline screening for thyroid disorders through RBSK. To initiate a national program for screening and treating hypothyroidism in pregnancy and follow national guidelines for screening of hypothyroidism released in 2014. To continue the national iodine deficiency disorders control program (started since 1987)
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Image 3. Echocardiography pictures showing large pericardial effusion.
3
Progress in Pediatric Cardiology xxx (xxxx) xxxx
A. Bableshwar and S. Mali
Acknowledgement [7]
I would like to thank Dr. Vivekanand S Gajapati, Head of Department, Cardiology for his expert advice and encouragement. I would also like to thank Dr. Kirti L for her support.
[8] [9]
References
[10]
[1] Bagcchi S. Hypothyroidism in India: more to be done. Lancet Diabetes Endocrinol 2014;2:778. [2] Wu T, Flowers JW, Tudiver F, Wilson JL, Punyasavatsut N. Subclinical thyroid disorders and cognitive performance among adolescents in the United States. BMC Pediatr 2006;6:12. [3] Lazar L, Frumkin RB, Battat E, Lebenthal Y, Phillip M, Meyerovitch J. Natural history of thyroid function tests over 5 years in a large pediatric cohort. J Clin Endocrinol Metab 2009;94:1678–82. [4] Purkait R, Prasad A, Bhadra R, Basu A. Massive pericardial effusion as the only manifestation of primary hypothyroidism. J Cardiovasc Dis Res 2013;4:248–50. [5] Ravinder Reddy K, Mudgalkar N, Sivarama Prasad L. A rare case of hypothyroidism presenting as massive pericardial effusion with cardiac tamponade. Perspect Med Res 2015;3(2):27–8. [6] Laulund AS, Nybo M, Brix TH, Abrahamsen B, Jørgensen HL, Hegedüs L. Duration of thyroid dysfunction correlates with all-cause mortality. The OPENTHYRO Register
[11]
[12] [13] [14] [15]
4
Cohort. PLoS One 2014;9(10):e110437https://doi.org/10.1371/journal.pone. 0110437. Dörr HV. Cardiovascular morbidity and mortality in thyroid dysfunction. Minerva Endocrinol 2005;30:199–216. Chaker L, Bianco AC, Jonklaas J, Peeters RP. Hypothyroidism. Lancet 2017;390:1550–62. Motabar A, Anousheh R, Shaker R, Pai RG. A rare case of amiodaroneinduced hypothyroidism presenting with cardiac tamponade. Int J Angiol 2011;20:177–80. Sondhi S, Bhardwaj R, Kandoria A, Ganju N, Mahajan K, et al. Massive pericardial effusion–rare and only presentation of hypothyrodism – myxedematous heart. J Cardiovasc Dis Diagn 2017;5:286. https://doi.org/10.4172/2329-9517.1000286. Bolin EH, Tang X, Lang SM, Daily JA, Collins RT. Characteristics of non-postoperative pediatric pericardial effusion: a multicenter retrospective cohort study from the Pediatric Health Information System (PHIS). Pediatr Cardiol 2018;39:347–53. https://doi.org/10.1007/s00246-017-1762-y. Marzuillo P, Grandone A, Perrotta S, et al. Very early onset of autoimmune thyroiditis in a toddler with severe hypothyroidism presentation: a case report. Ital J Pediatr 2016;42:61. Vigone MC, Capalbo D, Weber G, Salerno M. Mild hypothyroidism in childhood: who, when, and how should be treated? J Endocr Soc 2018;2:1024–39. Martinez-Soto T, Deal C, Stephure D, Trussell R, Boutin C, Djemli A, et al. Pericardial effusion in severe hypothyroidism in children. J Pediatr Endocrinol Metab 2010;23:1165–8. Chahine J, Ala CK, Gentry JL, et al. Pericardial diseases in patients with hypothyroidism. Heart 2019;105:1027–33.