title: Cancerous leptomeningitis and familial congenital hypopituitarism.
abstract: People are at higher risk of cancer as they get older or have a strong family history of cancer. The potential influence of environmental and behavioral factors remains poorly understood. Earlier population and case control studies reported that upper quartile of circulating IGF-I is associated with a higher risk of developing cancer suggesting possible involvement of the growth hormone (GH)/IGF system in initiation or progression of cancer. Since GH therapy increases IGF-1 levels, there have been concerns that GH therapy in hypopituitarism might increase the risk of cancer. We report a 42-year-old female patient who presented with subacute onset of symptoms of meningitis and with the absence of fever which resulted in death 70 days after the onset of symptoms. The patient together with her younger brother was diagnosed at the age of 5 years with familial congenital hypopituitarism, due to homozygous mutation c.150delA in PROP1 gene. Due to evolving hypopituitarism, she was replaced with thyroxine (from age 5), hydrocortisone (from age 13), GH (from age 13 until 17), and sex steroids in adolescence and adulthood. Her consanguineous family has a prominent history of malignant diseases. Six close relatives had malignant disease including her late maternal aunt with breast cancer. BRCA 1 and BRCA 2 mutational analysis in the patient's mother was negative. Histology after autopsy disclosed advanced ovarian cancer with multiple metastases to the brain, leptomeninges, lungs, heart, and adrenals. Low circulating IGF-1 did not seem to protect this patient from cancer initiation and progression in the context of strong family history of malignancies.
authors.affiliation: Clinic of Endocrinology, Clinical Center Serbia and Medical Faculty, University of Belgrade, Dr Subotic Str 13, 11000, Belgrade, Serbia.
authors.forename: S
authors.initials: S
authors.lastname: Vujovic
authors.affiliation: Clinical Center of Montenegro and Faculty of Medicine, University of Montenegro, Podgorica, Montenegro.
authors.forename: S
authors.initials: S
authors.lastname: Vujosevic
authors.affiliation: Clinical Center of Montenegro and Faculty of Medicine, University of Montenegro, Podgorica, Montenegro.
authors.forename: S
authors.initials: S
authors.lastname: Kavaric
authors.affiliation: Institute of Pathology, Medical Faculty, University of Belgrade, Belgrade, Serbia.
authors.forename: J
authors.initials: J
authors.lastname: Sopta
authors.affiliation: Clinic of Endocrinology, Clinical Center Serbia and Medical Faculty, University of Belgrade, Dr Subotic Str 13, 11000, Belgrade, Serbia.
authors.forename: M
authors.initials: M
authors.lastname: Ivovic
authors.affiliation: Aix-Marseille Université, CNRS, CRN2M UMR 7286, 13344, Marseille Cedex 15, France.|APHM, Hôpital Conception, Service d'Endocrinologie, Diabète et Maladies Métaboliques, Centre de Référence des Maladies Rares d'Origine Hypophysaire DEFHY, and Laboratoire de Biologie Moleculaire, GeOneE (Genetique Oncologique et Endocrinienne), 13385, Marseille Cedex 15, France.
authors.forename: A
authors.initials: A
authors.lastname: Saveanu
authors.affiliation: Aix-Marseille Université, CNRS, CRN2M UMR 7286, 13344, Marseille Cedex 15, France.|APHM, Hôpital Conception, Service d'Endocrinologie, Diabète et Maladies Métaboliques, Centre de Référence des Maladies Rares d'Origine Hypophysaire DEFHY, and Laboratoire de Biologie Moleculaire, GeOneE (Genetique Oncologique et Endocrinienne), 13385, Marseille Cedex 15, France.
authors.forename: T
authors.initials: T
authors.lastname: Brue
authors.affiliation: Department of Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK.
authors.forename: M
authors.initials: M
authors.lastname: Korbonits
authors.affiliation: Clinic of Endocrinology, Clinical Center Serbia and Medical Faculty, University of Belgrade, Dr Subotic Str 13, 11000, Belgrade, Serbia. popver@eunet.rs.
authors.forename: V
authors.initials: V
authors.lastname: Popovic
mesh_terms: D000328:Adult; D002277:Carcinoma / Q000556:secondary*; D017809:Fatal Outcome; D005260:Female; D013006:Growth Hormone / Q000172:deficiency; D018398:Homeodomain Proteins / Q000235:genetics; D020249:Hormone Replacement Therapy; D006801:Humans; D007018:Hypopituitarism / Q000151:congenital* / Q000188:drug therapy / Q000235:genetics; D055756:Meningeal Carcinomatosis / Q000556:secondary*; D010051:Ovarian Neoplasms / Q000473:pathology*; D010053:Ovary / Q000473:pathology; D010375:Pedigree
chemical_list: D018398:Homeodomain Proteins; C102134:Prophet of Pit-1 protein; D013006:Growth Hormone
keywords: Cancer; Familial congenital hypopituitarism; GH; IGF-I