Neelima Kharidehal, Srikanth Reddy D, H.V. Raghavendra Prasad
Children’s Medical Center, Krishna Institute of Medical Sciences, India

Address for correspondence: Neelima Kharidehal, Consultant Pediatrician and Intensivist, Lotus Children’s hospital, Lakdikapul, Hyderabad, A.P. State, India. E-mail: neelusatya@sify.com

Key words: Congenital, Neonatal, Hyperthyroidism, Thyrotoxicosis, Failure to thrive, Conjugated hyperbilirubinemia

A five-month-old female child born to consanguineous parents was admitted for inadequate weight gain, excessive irritability and frequent episodes of loose stools since birth. She was born to a third gravida mother at full term by Caesarean Section. Her birth weight was 3 kg. Before presenting to us, she was hospitalized thrice and extensively evaluated for failure to thrive, chronic diarrhea, jaundice and hepatosplenomegaly. Screening for Intrauterine infections (TORCH Profile) was performed thrice. Cytomegalovirus IgM was negative. Toxoplasma and Rubella IgM antibodies were was negative initially then became positive .

At admission into our hospital, her weight, length and head circumference were below the 5th percentile. She was febrile, pale, irritable and had oral candidiasis. Abdominal examination revealed a palpable liver of 3 cm below the right costal margin and a splenomegaly of 4 cm below the left costal margin. Examination of other systems was unremarkable. Fundus examination did not reveal any evidence of chorioretinitis and a BERA test was normal. She was adequately hydrated and commenced on intravenous ceftriaxone. Hypokalemia (serum potassium levels: 3.21 mEq/L), hypocalcemia (Serum total calcium level: 7 mg/dL) and coagulopathy were corrected. Treatment of cholestasis was commenced with oral choleretics (phenobarbitone & ursodeoxy cholic acid), fat soluble vitamin and calcium supplements. She was kept nil per orally for 48 hours and later commenced on lactose free formula through nasogastric tube. She was also commenced on oral probiotics (combination of: Streptococcus faecalis, Clostridium butyricum, Bacillus mesentericus, Lactibacillus sporogenes) and anti-secretory agent (Racecadotril). In view of the clinical presentation of Failure to thrive with excessive irritability, chronic diarrhea with persistent lactose intolerance, hepatosplenomegaly with intrahepatic cholestasis and an absence of stigmata suggestive of TORCH infections, a possibility of congenital hyperthyroidism was considered and her investigations were suggestive with elevated thyroid hormones and suppressed TSH. Further evaluation to delineate the etiology of congenital hyperthyroidism was not performed due to non-availability of the specific investigation (in India) and also financial constraints. Liver biopsy was contemplated initially but was deferred initially owing to the abnormal coagulation profile. Later on it was not performed as there was a good response to treatment with normalization of the liver function tests. A CT Scan Brain done at follow-up was normal with no evidence of intracranial calcification. HIV & Congenital syphilis were also negative. A BULIDA scan ruled out extrahepatic biliary atresia. Screening for inborn errors of metabolism was also performed twice. The screen revealed a normal amino acid profile except for an elevated homocysteine level. Cystic fibrosis, Galactosemia and Congenital adrenal hyperplasia were ruled out by appropriate investigations.

She was commenced on oral Propylthiouracil (7 mg/kg/day) and Lugol’s iodine (one drop thrice a day). Parents felt that the child was interacting well by 24 hours of start of medication with decreasing irritability. There were no loose stools by 48 hours. She was discharged after 8 days of admission. Weight recording on Day-23 after starting treatment revealed a catch-up growth of 54 grams/day of weight gain. Her thyroid assay and liver function tests normalized gradually. She is on regular follow-up and her developmental milestones are appropriate for age & sex at 12 months of age. Serial anthropometry recordings reveal an improving trend of growth with weight currently at the 5th centile for age & sex. Her head circumference is appropriate for the length.

Congenital hyperthyroidism (1) is a rare entity caused by transplacental passage of thyroid stimulating antibodies from the mother with Grave’s Disease (1-3). Dominantly inherited forms have also been described in the absence of maternal auto immunity because of activating mutations of TSH receptor(3-5)- non immune variant of congenital hyperthyroidism(6) as may be the case in our patient. The incidence of congenital hyperthyroidism is about one overt case for every 4000 to 50,000 deliveries. The mortality rate is high—12 to 20% (3,6,7). The most common cause of death is heart failure(2), other complications being tracheal compression by the goitrous thyroid and infections.

The effects of Congenital hyperthyroidism may begin in utero when it manifests as a growth retarded fetus. After birth, the symptoms are usually obvious by 10 days of life(8), but may be delayed because of maternal antithyroid drugs or coexisting blocking antibodies(9).

The common symptoms include goiter, neurological features like irritability, jitteriness, hyperkinesis, restlessness, failure to thrive inspite of hyperphagia, vomiting, diarrhea, excessive sweating and exophthalmos (1,2,3,6). It may also be associated with tachycardia, arrhythmias, systemic or pulmonary hypertension and congestive cardiac failure. The common signs include acral cyanosis, hepatosplenomegaly, lymphadenopathy, thymic hyperplasia, bruising and petechiae secondary to thrombocytopenia. Those affected may have advanced bone age, craniosynostosis and microcephaly. This child presented to us with failure to thrive, excessive irritability and chronic diarrhea

Excretion of the transplacentally acquired antibodies causes regression of signs and symptoms usually by 20 weeks (2). Remission is nearly always seen by 48 weeks (6). Nevertheless it can be persistent requiring long term treatment, probably owing to endogenous production of the Thyroid stimulating antibodies (2). In self limiting forms, nutritional support may be sufficient (1). In severe forms of the disease, Propyl thiouracil or methimazole may be utilized. Drug dosage should be titrated with the clinical response. To hasten resolution of symptoms, iodine preparations like Lugol’s iodine (1 drop thrice a day) may be used for the first 10 to 14 days In infants with congestive cardiac failure, Propranolol (2 mg/kg/day) can be used (1,2). Prednisolone ( 2mg/kg/day) suppresses peripheral deiodination of T4 to T3 and compensates for hypercatabolism of endogenous glucocorticoids induced by T3 and T4. Improvement in weight gain is considered as an indicator of adequate treatment. Anti thyroid drugs may be required for 4 to 12 weeks but some children do need prolonged therapy.

Hitherto, to the best of our knowledge, only one case of congenital hyperthyroidism with conjugated hyperbilirubinemia has been reported (10). Though hypothyroidism has conventionally been related to hyperhomocysteinemia(11), recent animal and human clinical studies have found a positive association between levels of thyroid hormones and homocysteine(12-14). This is probably caused by a functional vitamin B 12 and folate deficiency(12).

Thus in this child the clinical and biochemical profile was consistent with a diagnosis of congenital hyperthyroidism and more than anything else an appreciable response to anti thyroid drugs was confirmatory of the diagnosis. She is on regular follow-up and doing exceedingly well.

A thyroid profile is necessary in any child with failure to thrive with hepatosplenomegaly and chronic diarrhea.

Kharidehal N, Reddy SD, Raghavendra Prasad HV. A Five-Month-Old Female Child with Failure to Thrive, Excessive Irritability & Chronic Diarrhea. Pediatric Oncall [serial online] 2008 [cited 2008 ----------];5. Available from:
http://www.pediatriconcall.com/fordoctor/viewersChoice/chronic_diarrhea.asp