title: pNET co-secreting GHRH and calcitonin: ex vivo hormonal studies in human pituitary cells.
abstract: Acromegaly due to ectopic GHRH secretion from a neuroendocrine tumor (NET) is rare and comprises <1% of all acromegaly cases. Herein we present a 57-year-old woman with clinical and biochemical features of acromegaly and a 6 cm pancreatic NET (pNET), secreting GHRH and calcitonin. Following surgical resection of the pancreatic tumor, IGF1, GH and calcitonin normalized, and the clinical features of acromegaly improved. In vitro studies confirmed that the tumor secreted large amounts of both GHRH and calcitonin, and incubation of pNET culture-derived conditioned media stimulated GH release from a cultured human pituitary adenoma. This is a unique case of pNET secreting both GHRH and calcitonin. The ability of the pNET-derived medium to stimulate in vitro GH release from a human pituitary-cell culture, combined with the clinical and hormonal remission following tumor resection, confirmed the ectopic source of acromegaly in this patient.
  
  
  CONCLUSIONS
  Signs, symptoms and initial work-up of acromegaly due to ectopic GHRH secretion are similar to pituitary-dependent acromegaly. However, if no identifiable pituitary lesion is found, somatostatin receptor scan and further imaging (CT, MRI) should be performed.Detection of GHRH in the blood and in the tumor-derived medium supports the diagnosis of ectopic GHRH secretion.Functional bioactivity of pNET-secreted GHRH can be proved in vitro by releasing GH from human pituitary cells.
authors.affiliation: Endocrinology, Diabetes and Metabolic Unit, Kaplan Medical Center, Hebrew University Medical School of Jerusalem , Bilu 176100, Rehovot , Israel.
authors.forename: Taiba
authors.initials: T
authors.lastname: Zornitzki
authors.affiliation: Institute of Endocrinology and Felsenstein Medical Research Center, Rabin Medical Center, Petach Tikva, 49100, Israel; Sackler School of Medicine, Tel-Aviv University, Tel Aviv, 69978, Israel.
authors.forename: Hadara
authors.initials: H
authors.lastname: Rubinfeld
authors.affiliation: Endocrinology, Diabetes and Metabolic Unit, Kaplan Medical Center, Hebrew University Medical School of Jerusalem , Bilu 176100, Rehovot , Israel.
authors.forename: Lyudmila
authors.initials: L
authors.lastname: Lysyy
authors.affiliation: Endocrinology, Diabetes and Metabolic Unit, Kaplan Medical Center, Hebrew University Medical School of Jerusalem , Bilu 176100, Rehovot , Israel.
authors.forename: Tal
authors.initials: T
authors.lastname: Schiller
authors.affiliation: Laboratoire d'Hormonologie - CBPE, Hospices Civils de Lyon , 59 bd Pinel69677, Bron Cedex , France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Raverot
authors.affiliation: Institute of Endocrinology and Felsenstein Medical Research Center, Rabin Medical Center, Petach Tikva, 49100, Israel; Sackler School of Medicine, Tel-Aviv University, Tel Aviv, 69978, Israel.
authors.forename: Ilan
authors.initials: I
authors.lastname: Shimon
authors.affiliation: Endocrinology, Diabetes and Metabolic Unit, Kaplan Medical Center, Hebrew University Medical School of Jerusalem , Bilu 176100, Rehovot , Israel.
authors.forename: Hilla
authors.initials: H
authors.lastname: Knobler