Familial acromegaly due to aryl hydrocarbon receptor-interacting protein (AIP) gene mutation in a Turkish cohort Mutlu Niyazoglu • Muge Sayitoglu • Sinem Firtina • Esra Hatipoglu • Nurperi Gazioglu • Pinar Kadioglu Ó Springer Science+Business Media New York 2013 Abstract Aryl hydrocarbon receptor-interacting protein (AIP) is associated with 15–20 % of familial isolated pituitary adenomas and 50–80 % of cases with AIP muta- tion exhibit a somatotropinoma. Herein we report clinical characteristics of a large family where AIP R304X variants have been identified. AIP mutation analysis was performed on a large (n = 52) Turkish family across six generations. Sella MRIs of 30 family members were obtained. Basal pituitary hormone levels were evaluated in 13 family members harboring an AIP mutation. Thirteen of 52 family members (25 %) were found to have a heterozygous non- sense germline R304X mutation in the AIP gene. Seven of the 13 mutation carriers (53.8 %) had current or previous history of pituitary adenoma. Of these 7 mutation carriers, all but one had somatotropinoma/somatolactotropinoma (85.7 % of the pituitary adenomas). Of the 6 acromegaly patients with AIP mutation (F/M: 3/3) the mean age at diagnosis of acromegaly was 32 ± 10.3 years while the mean age of symptom onset was 24.8 ± 9.9 years. Three of the six (50 %) acromegaly cases with AIP mutation within the family presented with a macroadenoma and none pre- sented with gigantism. Biochemical disease control was achieved in 66.6 % (4/6) of the mutation carriers with acromegaly after a mean follow-up period of 18.6 ± 17.6 years. Common phenotypic characteristics of familial pituitary adenoma or somatotropinoma due to AIP mutation vary between families or even between individuals within a family. Keywords Familial pituitary adenoma Á Familial acromegaly Á Familial somatotropinoma Á AIP mutation Introduction Pituitary adenomas occur relatively common in the general population. Three different series confirm they are rela- tively common with a prevalence of 78–94:100,000 to 1:1,064 of the population [1–3]. Although they are invari- ably benign, pituitary adenomas have clinical significance since they are associated with hormone secretion or defi- ciencies and other complications due to local expansion and invasion. Acromegaly due to excess secretion of growth hormone (GH) constitutes 11–13.2 % of all pituitary ade- nomas, with a prevalence of 40–70 cases per million and incidence of 4 new cases per million population [1, 3, 4]. The overwhelming majority of pituitary adenomas are sporadic; however, familial adenomas have been identified, and account for up to 3–5 % of all cases [2, 3, 5, 6]. Recently, familial isolated pituitary adenomas (FIPA), which show an inherited pattern in the absence of multiple endocrine neoplasia 1 (MEN1) and Carney complex (CNC), have been defined. FIPA can be associated with hormone secretion or be nonfunctional. M. Niyazoglu Á E. Hatipoglu Á P. Kadioglu Division of Endocrinology and Metabolism, Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey M. Sayitoglu Á S. Firtina Department of Genetics, Institute for Experimental Medicine (DETAE), Istanbul University, Istanbul, Turkey N. Gazioglu Department of Neurosurgery, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey P. Kadioglu (&) Cerrahpasa Tip Fakultesi, IcHastaliklari Anabilim Dali, Endokrinoloji-Metabolizma ve Diyabet Bilim Dali, 34303 Cerrahpasa, Istanbul, Turkey e-mail: kadioglup@yahoo.com 123 Pituitary DOI 10.1007/s11102-013-0493-1