Precocious puberty in an infant with hepatoblastoma: a case report
© Al-Jumaily et al; licensee BioMed Central Ltd. 2011
Received: 18 May 2011
Accepted: 30 August 2011
Published: 30 August 2011
The syndrome of isosexual precocious puberty associated with primary malignant hepatic tumors is rare. All previously reported cases in the literature are old and prognosis was grim.
We present the case of a 15-month-old Asian male baby who presented with precocious puberty associated with hepatoblastoma. Serum concentrations of alpha-fetoprotein and free testosterone were elevated, as was beta human chorionic gonadotropin hormone. He was treated with six courses of chemotherapy and underwent surgery. His surface markers as well as free testosterone level returned to normal during therapy. The child has now been off therapy for 18 months with no evidence of tumor recurrence at follow-up.
Virilizing hepatoblastoma is rare and reported with poor outcome, but the development of new chemotherapeutic agents and complete surgical resection are promising.
Hepatoblastoma is the most common pediatric hepatic tumor. Using the current modalities of treatment, non-metastatic hepatoblastoma usually carries a favorable prognosis if completely resected. The tumor typically secretes α-fetoprotein (AFP) which is a useful marker for management and follow-up. On rare occasions, hepatoblastoma is associated with beta human chorionic gonadotropin hormone (β-hCG) secretion .
Paraneoplastic features of hepatoblastoma are not uncommon at presentation and include thrombocytosis and increased alkaline phosphatase . Occasionally, isosexual precocious puberty was reported in boys with hepatoblastoma [1, 3–15]. While most cases were reported in the 1980s, we believe documenting the response of similar cases to treatment in the modern era is important.
A 15-month-old Asian male baby presented to our center with precocious puberty and a hepatic mass. He was a product of cesarean section at 37 weeks of gestation. He had meconium aspiration at birth but had no history of hypoglycemia. His birth weight was 3.75 kg (in the 75th centile). At the age of eight months his mother noticed enlarging genitalia with sparse pubic hair and changes in his voice. These symptoms progressed over time and six months later, he started to have persistent fever and abdominal distension. A right upper quadrant mass was palpable at that time, so he was referred for evaluation. His family history was significant for an older sibling who died after being diagnosed with Wilms' tumor at the age of ten years and for a grandparent who died of lung cancer. There was no family history of overgrowth syndrome or other pediatric tumors. His parents were not related by blood.
Results of laboratory investigations during and after treatment
Free testosterone (pmol/L)
Normal values for age
At time of presentation
After first chemotherapy cycle
After second chemotherapy cycle
After fourth chemotherapy cycle
At end of therapy
Follow-up six months after end of therapy
Isosexual precocious puberty due to a virilizing hepatoblastoma is a rare but well documented occurrence [1, 3–15]. Cases have been confined to boys, generally below three years of age, who have usually presented with accelerated skeletal growth and virilization . Hepatic enlargement at presentation has been invariable.
Two hypotheses explaining androgen secretion are suggested in the literature: ectopic testosterone secretion and secondary testosterone secretion. The first theory suggests excess secretion of testosterone by neoplastic cells , while the second theory suggests secondary stimulation of the testes by β-hCG [3, 4, 7, 8]. While it remains difficult to speculate as to which may be the correct theory, it is interesting to notice that virilization occurred in all reported children with hepatoblastoma in association with elevated β-hCG levels, supporting the role of this hormone in excessive androgen production. Central and secondary precocious puberty such as hypothyroidism, premature adrenarche and congenital adrenal hyperplasia were first excluded by performing the appropriate tests. Together with elevated β-hCG levels and the findings of imaging studies, the correct diagnosis was suspected and proper therapy was initiated.
The majority of the previous cases were reported more than two decades ago, making it difficult to judge the outcome of virilizing hepatoblastoma, taking into consideration the inferior quality of imaging techniques, surgical techniques and chemotherapeutic regimens. As a matter of fact, it was suggested that virilizing hepatoblastoma carried a worse outcome when compared to nonvirilizing tumors, alluding to a unique biological setup . Our patient's response to therapy was favorable. His initial presentation with IVC thrombosis had put him at a higher risk for local failure; however, the favorable response to chemotherapy and complete resection is reassuring.
Although isosexual precocious puberty with hepatoblastoma is rare and carries a poor outcome (as reported in most cases), results due to developments in chemotherapeutic agents and complete surgical resection are promising.
Written informed consent was obtained from the patient's legal guardian (father) for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
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