title: Variability in quantitative expression of receptors in nonfunctioning pituitary macroadenomas--an opportunity for targeted medical therapy.
abstract: OBJECTIVE
  The surgical removal of a nonfunctioning pituitary macroadenoma (NFP-Mac) is often incomplete. The appropriate treatment of recurrent/residual NFP-Macs is not well established. Our objective was to detect and quantify receptors that may serve as potential targets for medical therapy for NFP-Macs with postsurgical residuals.
  
  
  METHODS
  Several classes of pituitary receptors were analyzed by quantitative reverse transcriptase-polymerase chain reaction in 17 adult NFP-Mac patients who underwent surgery.
  
  
  RESULTS
  The median age was 50 years, and 76% of patients were male. On magnetic resonance imaging, the mean NFP-Mac diameter was 3.3 ± 1.02 cm. Somatostatin receptor (SSTR) and dopamine receptor (DR) subtypes were found in almost all tumors. Based on previous studies, we postulated a cutoff of ≥ 2,000 receptor copies at which a response to therapy may occur. This cutoff was found in SSTR3 in 3 patients, SSTR2 in 2 patients, SSTR1 and SSTR5 in 1 patient each, DR(2_total) in 13 patients, DR(2_short) (considered the most responsive to dopamine agonists) in 10 patients, and DR(2_long), DR5, DR4, and DR1 in 7, 3, 2, and 1 patient, respectively. Tumor size, invasiveness score, immunochemistry, gender, age, clinical symptoms, and postoperative residual tumor growth did not correlate with the type or copy number of receptor mRNAs.
  
  
  CONCLUSIONS
  NFP-Macs with significant postsurgical tumor residuals contain several DR and SSTR subtypes, some with high copy numbers. The receptor composition of NFP-Macs may guide future clinical research into targeted treatment strategies to reduce residual tumor volume. Such studies would determine the potential threshold of receptor levels for response to therapy for existing dopaminergic agonists and somatostatin analogs.
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, John Stroger Hospital of Cook County, Chicago, Illinois Rush University Medical Center, Chicago, Illinois.
authors.forename: Ambika
authors.initials: A
authors.lastname: Babu
authors.affiliation: Department of Cell Biology, Physiology, and Immunology, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/Hospital Universitario Reina Sofia, University of Cordoba and CIBER de la Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, Spain.
authors.forename: Raul M
authors.initials: RM
authors.lastname: Luque
authors.affiliation: Neurosurgery and Anatomy and Cell Biology, Rush University, University of Illinois at Chicago, Illinois.
authors.forename: Roberta
authors.initials: R
authors.lastname: Glick
authors.affiliation: Department of Pathology, John Stroger Hospital of Cook County, Chicago, Illinois.
authors.forename: Manuel
authors.initials: M
authors.lastname: Utset
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, John Stroger Hospital of Cook County, Chicago, Illinois Rush University Medical Center, Chicago, Illinois.
authors.forename: Leon
authors.initials: L
authors.lastname: Fogelfeld
mesh_terms: D000236:Adenoma / Q000737:chemistry* / Q000188:drug therapy / Q000473:pathology; D000328:Adult; D018491:Dopamine Agonists / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000737:chemistry* / Q000188:drug therapy / Q000473:pathology; D011446:Prospective Studies; D011954:Receptors, Dopamine / Q000032:analysis; D017481:Receptors, Somatostatin / Q000032:analysis
chemical_list: D018491:Dopamine Agonists; D011954:Receptors, Dopamine; D017481:Receptors, Somatostatin