First report of ectopic ACTH syndrome and PTHrP-induced hypercalcemia due to a hepatoblastoma in a child.

Department of Pediatrics, Klinikum rechts der Isar, Technische Universität München, Kölner Platz 1, D-80804 Munich, Germany.
European Journal of Endocrinology (Impact Factor: 3.69). 04/2010; 162(4):813-8. DOI: 10.1530/EJE-09-0961
Source: PubMed

ABSTRACT Only occasionally, endocrine-active tumors develop directly from hepatic tissue, and may lead to paraneoplastic syndromes (PNS). PNS mostly accompany malignancy of adulthood and are exceedingly rare in children.
A girl aged 6 years and 9 months presented with a 2-month history of rapidly progressive weight gain, abdominal distension, and polyuria/pollakiuria accompanied by short episodes of abdominal pain. She showed the typical clinical features of Cushing's syndrome and a huge hepatic mass. An abdominal computed tomography (CT) scan revealed a large liver tumor. Blood glucose and serum calcium were greatly elevated.
Case report describing the causative relationship of the clinical findings.
Physical examination; ultrasound of the abdomen; CT scan of the abdomen and the chest; conventional X-rays; routine hematology; blood chemistry and multiple parameters of calcium and phosphorus metabolism; multisteroid analysis in serum and urine; adrenocortical stimulation and suppression tests; histopathological assessment of the resected tumor; immunohistochemistry for ACTH, beta-endorphin, corticotrophin-releasing hormone (CRH), and PTH-related peptide (PTHrP); electron microscopy of tumor cells; ACTH and CRH extraction from the tumor tissue; and clinical follow-up for more than 20 years.
Giant hepatoblastoma (HB; approximately 1000 ml volume) of the right lobe of the liver with combined ectopic ACTH syndrome and PTHrP-induced tumor-associated hypercalcemia. Wide local excision and polychemotherapy led to complete reversal of the paraneoplastic phenotype.
This is the first report of an endocrine-active HB causing both Cushing's syndrome and PTHrP-related 'humoral hypercalcemia of malignancy'. This information should be added to the well-known beta-human chorionic gonadotropin-related paraneoplastic effects of HB in children.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Ectopic ACTH syndrome (EAS) is rare in children and is challenging to differentiate from Cushing's disease. A 9-year-old boy presented with a history of worsening fatigue, muscle weakness, weight gain and acne, and he appeared cushingoid with central obesity and hyperpigmentation of his palmar creases. Investigations demonstrated an elevated ACTH and an elevated morning cortisol that did not suppress with low or high dose dexamethasone suppression tests. Brain imaging inconsistently showed a small pituitary lesion. Chest and abdomen computed tomography (CT) showed adrenal hyperplasia and a liver hemangioma. [18F]fluorodeoxyglucose positron emission tomography CT was normal. Ultrasound and abdominal magnetic resonance imaging (MRI) also showed a liver hemangioma. Bilateral inferior petrosal sinus sampling, however, was consistent with ectopic ACTH production. An octreotide scan revealed a small focus of increased activity in the liver, which was the likely source of ectopic ACTH production. The patient was managed with metyrapone followed by a wedge liver resection. Pathology showed a well-differentiated neuroendocrine tumor (NET) that stained positive for ACTH. Post-operatively, the signs and symptoms of EAS are resolving and his hypothalamic-pituitary-adrenal axis is recovering. This case describes the first pediatric patient with EAS caused by a liver NET. It illustrates the challenges in localizing the source of ectopic ACTH and treating this rare condition.
    Journal of pediatric endocrinology & metabolism: JPEM 04/2013; 26(7-8):1-3. DOI:10.1515/jpem-2012-0337 · 0.71 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Imaging plays a pivotal role in the diagnosis and management of children with hepatoblastoma. However, the continuing evolution of imaging technologies and rarity of hepatoblastoma make validation of imaging approaches challenging. In Europe and other parts of the world staging of hepatoblastoma is based on imaging features while in North America it is based on surgical resectability. In this review we discuss the clinical and imaging features that aid in diagnosing and monitoring children with hepatoblastoma. The potential roles of new imaging techniques are presented, and differences between staging systems are addressed. Pediatr Blood Cancer 2012; 59: 793-799. © 2012 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 11/2012; 59(5):793-9. DOI:10.1002/pbc.24221 · 2.35 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Childhood cancer is the leading cause of death by disease among U.S. children between infancy and age 15. Despite successes in treating solid tumors such as Wilms tumor, disappointments in the outcomes of high-risk solid tumors like neuroblastoma have precipitated efforts towards the early and accurate detection of these malignancies. This review summarizes available solid tumor serum biomarkers with a special focus on mediastinal and abdominal cancers in children.
    International Journal of Molecular Sciences 12/2012; 13(1):1126-53. DOI:10.3390/ijms13011126 · 2.34 Impact Factor