A forty-five-day-old female infant presented with prolonged jaundice with clinical features suggestive of congenital hypothyroidism (CHT). On investigations, the infant was noted to have indirect hyperbilirubinemia (13.8 mg/dl) with increased levels of AST (298 IU/dl) and ALT (174 IU/dl) in the serum. The child had low levels of free T3 (<1 pg/ml) and free T4 (0.4 ng/dl) secondary to thyroid agenesis detected on radionuclide scan and ultrasonography of the neck and raised levels of TSH (>500 microIU/ml) in the serum. The combination of indirect hyperbilirubinemia and raised levels of hepatic transaminases has not been reported in babies with CHT. Following institution of oral thyroxin therapy, the serum bilirubin levels ameliorated (2.9 mg/dl) considerably by 15 days of therapy and the serum levels of AST (40 IU/dl) and ALT (20 IU/dl) got normalized. The case demonstrates that raised levels of hepatic transaminases can occur in infants with CHT and these can resolve just with thyroxin therapy, obviating the need for extensive investigative laboratory work-up.
As neonatal screening program is not implemented in several resource-poor settings, babies with congenital hypothyroidism (CHT) present with a spectrum of clinical manifestations of varying severity [
A 45-day-old exclusively breastfed female infant born at term (birth weight: 3033 g) vaginally to a healthy mother, presented with jaundice noticed since the sixth day of life. The jaundice that was not associated with clay colored stools or high colored urine increased progressively and was associated with constipation and excessive sleepiness. There was no history of hypothyroidism in the mother nor had she consumed any drugs other than hematinics during the ante-natal period. Both mother’s and baby’s blood group was O positive. The mother was negative for hepatitis B surface antigen (HBsAg) during pregnancy. On examination, the infant was hemodynamically stable (pulse 122/min, BP: 68/42 mm Hg, no cold extremities), weighed 3.5 kg (at third percentile, WHO Child Growth Standards), and had a length of 52 cm (between 3rd and 50th percentile, WHO Child Growth Standards; upper : lower segment ratio: 1.6). She had coarse facies, open posterior fontanel (2 mm
The clinical diagnosis of neonatal hyperbilirubinemia in a child with CHT was confirmed with laboratory investigations (Table
Results of serial biochemical investigations.
Day of life | Reference value | 44 | 51 | 52 | 55 | 59 | 70 |
---|---|---|---|---|---|---|---|
Day following initiation of therapy | −11 | −4 | −3 | 0 | 4 | 15 | |
Serum bilirubin (total) | <1.2 mg/dl | 14.9 | 16 | 15.2 | 14.6 | 16.3 | 3.8 |
Serum bilirubin (direct) | <0.2 mg/dl | 1.1 | 1.3 | 1.3 | 1.3 | 1.1 | 0.9 |
Serum bilirubin (indirect) | | 13.8 | 14.7 | 13.9 | 13.3 | 15.2 | 2.9 |
Serum protein, total | 5.1–7.3 g/dl | — | 5.6 | 5.3 | 5.6 | 5.7 | 6.0 |
Serum albumin | 2.2–4.8 | — | 3.4 | 3.3 | 3.4 | 3.6 | 4.1 |
SGOT (AST) | 9–80 u/l | — | 298 | 278 | 225 | 220 | 40 |
SGPT (ALT) | 13–45 u/l | — | 174 | 157 | 148 | 135 | 20 |
Serum alkaline phosphatase | 150–420 u/l | — | 239 | 213 | 226 | 221 | 247 |
Serum free T3 | 0.91–4.4 pg/ml | — | — | — | <1 | — | 4.1 |
Serum free T4 | 0.8–2.0 ng/dl | — | — | — | <0.4 | — | 1.4 |
TSH | 0.8–8.2 microIU/ml | — | — | — | 500 | — | 37.8 |
This communication describes an infant with congenital hypothyroidism with prolonged indirect jaundice and persistently increased levels of hepatic transaminases (AST and ALT). When treated with L-thyroxin, most of the biochemical abnormalities normalized within 15 days of therapy and TSH levels decreased significantly. The association between congenital hypothyroidism (CHT) and neonatal (conjugated or unconjugated) hyperbilirubinemia is long established. A few cases of CHT with unconjugated hyperbilirubinemia have raised levels of hepatic transaminases in the blood, which resolve following treatment with thyroxin [
Despite extensive literature search, we could not locate any case of CHT with indirect hyperbilirubinemia and raised levels of hepatic transaminases. When associated with conjugated hyperbilirubinemia, the raised transaminase levels in infants with CHT are attributed to cholestasis. Our case suggests that raised transaminase levels might be occurring independent of hepatic involvement. In this context, it is worthwhile remembering that although liver is an overwhelmingly predominant source of transaminases, there are other sources of AST (cardiac and skeletal muscles, kidneys, brain, pancreas, lungs, and erythrocytes) and ALT (skeletal muscle and kidneys). It is also well-known that myriad myopathies are associated with raised levels of AST/ALT and that these abnormal levels could precede clinical manifestations of myopathy by several weeks [
This case report has practical implications: the case indicates that presence of raised transaminase levels in infants with CHT does not necessarily indicate presence of liver diseases and hence there is no need to subject such infants to invasive diagnostic tests. We also hope that this report will motivate others to report such cases in their practice, which would provide credence to the notion of this being a real association.
The authors declare that they have no competing interests.
Ruchi Mantri was responsible for collection of data, literature search, clinical care, conceptualization, preparation of the initial draft, and approval of the final draft. S. B. Bavdekar was responsible for literature search, clinical care, conceptualization, intellectual inputs for improvement in the manuscript draft, and approval of the final draft. Sushma U. Save was responsible for clinical care, conceptualization, preparation of the initial draft, and approval of the final draft.