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 Table of Contents  
CASE REPORT
Year : 2016  |  Volume : 5  |  Issue : 3  |  Page : 202-204

Isolated central hypothyroidism presenting with severe cholestasis, hepatosplenomegaly, and pallor: A case report and review of literature


1 Department of Pediatric Medicine, Division of Neonatology, Medical College, Kolkata, West Bengal, India
2 Department of Pediatric Medicine, Medical College, Kolkata, West Bengal, India

Date of Web Publication28-Sep-2016

Correspondence Address:
Dr. Arijit Bhowmik
6, Kulada Roy Lane, Khagra, Murshidabad - 742 103, West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2249-4847.191268

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  Abstract 

Prolonged neonatal jaundice has been previously reported in neonates with congenital hypothyroidism. Isolated central hypothyroidism is a rare disease which may be missed by newborn screening programs. Here, we report a case of isolated central hypothyroidism presenting with neonatal hyperbilirubinemia, anemia, and hepatosplenomegaly, which showed marked improvement with levothyroxine supplementation.

Keywords: Cholestasis, hepatosplenomegaly, isolated central hypothyroidism


How to cite this article:
Bhowmik A, Biswas T. Isolated central hypothyroidism presenting with severe cholestasis, hepatosplenomegaly, and pallor: A case report and review of literature. J Clin Neonatol 2016;5:202-4

How to cite this URL:
Bhowmik A, Biswas T. Isolated central hypothyroidism presenting with severe cholestasis, hepatosplenomegaly, and pallor: A case report and review of literature. J Clin Neonatol [serial online] 2016 [cited 2019 Dec 6];5:202-4. Available from: http://www.jcnonweb.com/text.asp?2016/5/3/202/191268


  Introduction Top


Congenital hypothyroidism (CH) remains one of the most important causes of preventable mental retardation. CH may be primary, due to thyroid agenesis/dysgenesis or dyshormonogenesis or secondary (central). Central hypothyroidism is generally associated with other pituitary hormone deficiencies (e.g., due to septo-optic dysplasia). Isolated deficiency of thyroid-stimulating hormone (TSH) is extremely rare.[1] Nonspecific and subtle clinical presentations often delay the diagnosis of CH, due to any etiology. Neonatal hyperbilirubinemia has been reported to be a common presentation of CH.[2] Here, we report a case of isolated central hypothyroidism presenting with neonatal hyperbilirubinemia, anemia, and hepatosplenomegaly, which subsequently improved with levothyroxine supplementation.


  Case Report Top


A 3-day-old term female neonate with birth weight of 2.5 kg was admitted for icterus with sole staining. The neonate had ABO incompatibility (mother's blood group was O+ve and neonate's blood group was A+ve ) with a total serum bilirubin (TSB) of 24 mg/dl (direct 1.3 mg/dL, indirect 22.7 mg/dL) on admission. Peripheral smear examination revealed normal red blood cell morphology with no evidence of hemolysis. Direct Coombs test was negative, and reticulocyte count was normal. Double-volume exchange transfusion was done with O+ve whole blood on the same day. After exchange transfusion, TSB decreased to 12.5 mg/dl. However, on day 4, TSB again increased to 16.8 mg/dl and thereafter continued increasing progressively to finally reach 35.5 mg/dl (direct 24 mg/dL, indirect 10.9 mg/dL) on day 10. Liver enzymes and albumin were normal. There was clinical pallor with a hemoglobin level of 6.5 g/dl, requiring 15 ml/kg packed red blood cell transfusion. At that time, the neonate was lethargic but hemodynamically stable, without any respiratory distress. There was progressive hepatosplenomegaly. Sepsis screen was negative, there was no growth in blood culture, and cerebrospinal fluid analysis was not suggestive of meningitis. Ultrasonography of whole abdomen was normal apart from hepatosplenomegaly. There was no evidence suggestive of biliary atresia. The neonate was normoglycemic during the entire course of illness, with a normal blood pH and serum electrolytes. Screenings for TORCH infections and urine nonglucose reducing substance were negative. fT4 (0.78 ng/100 mL, reference 0.9-2.6 ng/100 mL) and TSH (0.04 μIU/mL, reference 1.36-8.8 μIU/mL) values were low. Serum levels of cortisol (9.7 mcg/dL, reference 3.7-19.4 mcg/dL), adrenocorticotropic hormone (ACTH) (38 pg/mL, reference 10-60 pg/mL) growth hormone (GH) (21.76 ng/mL, reference: 5-40 ng/mL) measured at 8:00 am were normal. Ultrasonography of brain did not suggest any detectable abnormality. There was no evidence of thyroid agenesis/dysgenesis on ultrasonography. Magnetic resonance imaging of brain with special emphasis for pituitary hypophyseal area was normal. Hence, it was diagnosed as a case of neonatal cholestasis due to isolated central hypothyroidism. Thyrotropin-releasing hormone (TRH) stimulation test and genetic analyses could not be carried out due to financial constraints.

Levothyroxine supplementation was started with 15 mcg/kg/day dose. There was dramatic response after starting levothyroxine. Activity improved on the next day and TSB came down to 4.2 mg/dL (direct 2.7 g/dL) within 4 days. The neonate was discharged and was asked for a follow-up. Hepatosplenomegaly resolved within 4 months. On the last 1-year follow-up, fT4 is within normal range with thyroxin replacement and TSH remained very low. There is no further pallor. Growth and development of the neonate are normal.


  Discussion Top


Congenital central hypothyroidism is a rare entity, affecting 1:80,000-1:120,000 persons,[3] caused by defects at either the pituitary (secondary hypothyroidism) or hypothalamus (tertiary hypothyroidism) levels. It can exist as a part of combined hypopituitarism, or can be isolated, with the latter being more difficult to detect because of the absence of signs of other hormonal deficiencies such as hypoglycemia.[4] Mutations in the TSH-β subunit or the TRH receptor gene account for the most of the cases.[4] Our case again emphasizes the established fact that screening program should not only be based on TSH but also should include fT4 also.

In our case, the neonate presented with unconjugated hyperbilirubinemia, in the backdrop of ABO incompatibility. However, after double-volume exchange transfusion, she developed conjugated hyperbilirubinemia, along with pallor and hepatosplenomegaly, which improved with levothyroxine supplementation. A diagnosis of isolated central hypothyroidism was made based on low values of both fT4 and TSH, in the presence of normal serum levels of GH, ACTH, and cortisol.

Prolonged neonatal jaundice is known to be an important clinical sign of CH. Kurtoğlu et al., in 2009, reported a case of neonatal sludge in CH.[2] Although the exact pathophysiology of cholestasis in CH remains to be elucidated, postulated mechanisms include the pro-relaxant effect of thyroid hormones on  Sphincter of Oddi More Details[5] and the consequent decrease in bile flow in hypothyroidism.[6] Anemia was an important finding in our case, and it has been previously reported to coexist with CH.[7] Thyroid hormone deficiency has been shown to decrease clonogenic potential of erythrocyte-burst forming units,[8] which might explain, at least in part, the accompanying anemia.

Karnsakul et al.[9] reported hepatosplenomegaly and cholestasis to be common in congenital hypopituitarism. They found that in majority of cases in their series, resolution of cholestasis and hepatosplenomegaly occurred after glucocorticoid and thyroid hormone replacement. In our case also, a dramatic response was seen with initiation of levothyroxine supplementation, with complete resolution of hepatosplenomegaly occurring within 16 weeks. However, unlike that reported by Karnsakul et al.,[10] there was no elevation of transaminases in our case. The mechanism of hepatosplenomegaly in hypopituitarism is not yet fully understood, but a role of hematopoiesis has been suggested.[9],[10]


  Conclusion Top


It may be said that second pathology, even if it is rare, must be searched if there is clinical deterioration after treatment for the first pathology. Isolated central hypothyroidism, though rare, might be an important cause of prolonged neonatal jaundice. A low threshold of suspicion is necessary to diagnose this condition because of its potential to be missed by most newborn screening programs.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Rastogi MV, LaFranchi SH. Congenital hypothyroidism. Orphanet J Rare Dis 2010;5:17.  Back to cited text no. 1
[PUBMED]    
2.
Kurtoglu S, Coban D, Akin MA, Akin L, Yikilmaz A. Neonatal sludge: A finding of congenital hypothyroidism. J Clin Res Pediatr Endocrinol 2009;1:197-200.  Back to cited text no. 2
    
3.
Lania A, Persani L, Beck-Peccoz P. Central hypothyroidism. Pituitary 2008;11:181-6.  Back to cited text no. 3
[PUBMED]    
4.
Grünert SC, Schmidts M, Pohlenz J, Kopp MV, Uhl M, Schwab KO. Congenital central hypothyroidism due to a homozygous mutation in the TSHß subunit gene. Case Rep Pediatr 2011;2011:369871.  Back to cited text no. 4
    
5.
Inkinen J, Sand J, Arvola P, Pörsti I, Nordback I. Direct effect of thyroxine on pig sphincter of oddi contractility. Dig Dis Sci 2001;46:182-6.  Back to cited text no. 5
    
6.
Laukkarinen J, Sand J, Saaristo R, Salmi J, Turjanmaa V, Vehkalahti P, et al. Is bile flow reduced in patients with hypothyroidism? Surgery 2003;133:288-93.  Back to cited text no. 6
[PUBMED]    
7.
Franzese A, Salerno M, Argenziano A, Buongiovanni C, Limauro R, Tenore A. Anemia in infants with congenital hypothyroidism diagnosed by neonatal screening. J Endocrinol Invest 1996;19:613-9.  Back to cited text no. 7
    
8.
Kawa MP, Grymula K, Paczkowska E, Baskiewicz-Masiuk M, Dabkowska E, Koziolek M, et al. Clinical relevance of thyroid dysfunction in human haematopoiesis: Biochemical and molecular studies. Eur J Endocrinol 2010;162:295-305.  Back to cited text no. 8
[PUBMED]    
9.
Karnsakul W, Sawathiparnich P, Nimkarn S, Likitmaskul S, Santiprabhob J, Aanpreung P. Anterior pituitary hormone effects on hepatic functions in infants with congenital hypopituitarism. Ann Hepatol 2007;6:97-103.  Back to cited text no. 9
    
10.
Herman SP, Baggenstoss AH, Cloutier MD. Liver dysfunction and histologic abnormalities in neonatal hypopituitarism. J Pediatr 1975;87(6 Pt 1):892-5.  Back to cited text no. 10
    




 

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