title: Treatment-resistant pediatric giant prolactinoma and multiple endocrine neoplasia type 1.
abstract: BACKGROUND
  Pediatric pituitary adenomas are rare, accounting for <3 % of all childhood intracranial tumors, the majority of which are prolactinomas. Consequently, they are often misdiagnosed as other suprasellar masses such as craniopharyngiomas in this age group. Whilst guidelines exist for the treatment of adult prolactinomas, the management of childhood presentations of these benign tumors is less clear, particularly when dopamine agonist therapy fails. Given their rarity, childhood-onset pituitary adenomas are more likely to be associated with a variety of genetic syndromes, the commonest being multiple endocrine neoplasia type 1 (MEN-1).
  
  
  METHODS
  We present a case of an early-onset, treatment-resistant giant prolactinoma occurring in an 11-year-old peripubertal boy that was initially sensitive, but subsequently highly resistant to dopamine agonist therapy, ultimately requiring multiple surgical debulking procedures and proton beam irradiation. Our patient is now left with long-term tumor- and treatment-related neuroendocrine morbidities including blindness and panhypopituitarism. Only after multiple consultations and clinical data gained from 20-year-old medical records was a complex, intergenerationally consanguineous family history revealed, compatible with MEN-1, with a splice site mutation (c.784-9G > A) being eventually identified in intron 4 of the MEN1 gene, potentially explaining the difficulties in management of this tumor. Genetic counseling and screening has now been offered to the wider family.
  
  
  CONCLUSIONS
  This case emphasizes the need to consider pituitary adenomas in the differential diagnosis of all pediatric suprasellar tumors by careful endocrine assessment and measurement of at least a serum prolactin concentration. It also highlights the lack of evidence for the optimal management of pediatric drug-resistant prolactinomas. Finally, the case we describe demonstrates the importance of a detailed family history and the role of genetic testing for MEN1 and AIP mutations in all cases of pediatric pituitary adenoma.
authors.affiliation: Section for Genetics and Epigenetics in Health and Disease, Genetics and Genomic Medicine Programme, University College London Institute of Child Health, 30 Guilford Street, London, WC1N 1EH UK ; The London Centre for Pediatric Endocrinology & Diabetes, Neuroendocrine Division, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street, London, WC1N 3JH UK.
authors.forename: Hoong-Wei
authors.initials: HW
authors.lastname: Gan
authors.affiliation: Section for Experimental & Personalized Medicine, Genetics & Genomic Medicine Programme, University College London Institute of Child Health, 30 Guilford Street, London, WC1N 1EH UK.
authors.forename: Chloe
authors.initials: C
authors.lastname: Bulwer
authors.affiliation: Department of Neurosurgery, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street, London, WC1N 3JH UK.
authors.forename: Owase
authors.initials: O
authors.lastname: Jeelani
authors.affiliation: Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, 34th and Civic Center Boulevard, Philadelphia, PA 19104 USA ; Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, 34th and Civic Center Boulevard, Philadelphia, PA 19104 USA.
authors.forename: Michael Alan
authors.initials: MA
authors.lastname: Levine
authors.affiliation: Centre for Endocrinology, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ UK.
authors.forename: Márta
authors.initials: M
authors.lastname: Korbonits
authors.affiliation: The London Centre for Pediatric Endocrinology & Diabetes, Neuroendocrine Division, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street, London, WC1N 3JH UK.
authors.forename: Helen Alexandra
authors.initials: HA
authors.lastname: Spoudeas
keywords: Familial prolactinoma; Macroprolactinoma; Multiple endocrine neoplasia type 1; Pituitary neoplasms; Survivorship