SFEBES2009 Oral Communications Thyroid, reproduction and endocrine tumours (8 abstracts)
The clinical and genetic characteristics of patients with familial isolated pituitary adenoma
H Chahal 1 , S Igreja 1 , M Gueorguiev 1 , R Quinton 2 , J Wass 3 , V Popovic 4 , A Ribeiro-Oliveira Jr 5 , J Monson 1 , S Akker 1 , P Gallego 6 , S Orme 7 , A Goldstone 8 , J Bevan 9 , T Cheetam 10 , J Davis 11 , R Clayton 12 , D Flanagan 13 , L Frohman 14 , A Grossman 1 & M Korbonits 1
1Barts and the London Medical School, Centre for Endocrinology, London, UK; 2Department of Endocrinology, Royal Victoria Infirmary and University of Newcastle-upon-Tyne, Newcastle-Upon-Tyne, UK; 3Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK; 4Department of Endocrinology, University Clinical Center, Belgrade, Serbia; 5Department of Internal Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil; 6Department of Endocrinology, Perth, Australia; 7Department of Endocrinology, Leeds, UK; 8Department of Endocrinology, Hammersmith Hospital, London, UK; 9Department of Endocrinology, Aberdeen, UK; 10Department of Endocrinology, Newcastle-Upon-Tyne, UK; 11Department of Endocrinology, University of Manchester, Manchester, UK; 12Department of Endocrinology, University Hospital of North Staffordshire, Stoke-On-Trent, UK; 13Department of Endocrinology, Derriford Hospital, Plymouth, UK; 14Section of Endocrinology, Metabolism and Diabetes, University of Illinois at Chicago, Chicago, UK.
Background: Familial pituitary adenomas can occur in the classic syndromes of MEN-1 and Carney complex. Recently an autosomal dominant disease with incomplete penetrance has been described as ‘familial-isolated-pituitary-adenoma’ (FIPA). Previous studies of familial acromegaly and gigantism disclosed germline mutations in the AIP gene located in the previously suspected chromosome 11q13 region.
Aims: To analyse the prevalence of AIP-mutations in our large FIPA cohort and to evaluate the clinical characteristics of FIPA patients with or without AIP-mutations.
Methods: We studied 39 FIPA families and identified 97 pituitary tumour patients.
Results: Our FIPA cohort had 52 (54%) males and 45 (46%) females with the mean (±S.D.) age at diagnosis 33.3±15.1 year. Eleven families had a germline AIP-mutation with missense, nonsense, splice-site and the first known promoter mutation. While mutations resulting in complete disruption of the AIP-protein were scattered over the whole gene, point mutations only affected the C-terminal-protein-binding domain. Fifty-three individuals had a heterozygote germline AIP-mutation, with 36 (68%) having clinical disease, although not all family members were available for genotyping. Patients with AIP-mutations had a mean age of diagnosis significantly lower than those without AIP-mutations: 24.5±10.9 vs 40.0±14.9 year (P<0.001). Macroadenomas occurred in 93% patients with AIP-mutations versus 84% patients without AIP-mutations. A poor biochemical response to somatostatin analogues (<50% reduction in GH/IGF-I) occurred in 8/15 families with acromegaly. Non-pituitary tumours were observed in 7 families containing affected patients or obligate AIP-mutation carriers:lipomas, ependymoma, anaplastic astrocytoma, breast, thyroid, testicular and bone marrow tumours. Out the FIPA cohort, there were 23 families containing 22 patients with gigantism, of which 17 (77%) had AIP-mutations.
Conclusions: AIP-mutations were identified in 11 families of our FIPA cohort occurring in families with somatotroph adenomas. Patients with AIP-mutations have clinical disease significantly earlier than those patients without AIP-mutations, and may respond less well than other patients to somatostatin analogues.
Volume 19
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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