title: Hormone secretion by pituitary adenomas is characterized by increased disorderliness and spikiness but more regular pulsing.
abstract: BACKGROUND
  Hormone secretion by functioning pituitary tumors is characterized by increased basal (nonpulsatile) secretion, enhanced pulse frequency, amplified pulse mass, and increased disorderliness.
  
  
  OBJECTIVE
  The objective of the study was to quantify (subtle) abnormalities of hormone secretion by pituitary adenomas and the influence of selective pituitary surgery and suppressive medications on these parameters.
  
  
  METHODS
  Approximate entropy (ApEn) was quantified with a refined algorithm, spikiness by a new method to evaluate sudden short-lived increases in hormone levels, and pulsing regularity, determined with a fully automated deconvolution program. These 3 distinct measures of secretory disruption were compared in untreated and treated patients with acromegaly, prolactinoma, and Cushing's disease together with matching profiles in healthy controls.
  
  
  RESULTS
  ApEn and spikiness were markedly increased in all untreated patient groups and normalized after pituitary surgery in acromegaly and hypercortisolism. In contrast, hormone-suppressive medical treatment in acromegaly and prolactinoma did not normalize ApEn. Spikiness normalized in acromegalic patients but not in prolactinoma. GH and cortisol pulsing regularity was elevated in acromegaly and Cushing's disease, respectively, and normalized after surgery. Medical treatment caused normalization of pulsing regularity in acromegaly but not in prolactinoma patients.
  
  
  CONCLUSIONS
  This study extends the understanding of disorganized hormone secretion by hyperfunctioning pituitary adenomas. The new findings are increased spikiness in all 3 tumor groups and increased pulsing regularity in GH- and ACTH-secreting adenomas. The mechanisms behind the marked pattern irregularity and the selective normalization by surgical and medical therapies are not established yet but may include diminished feedback signaling in addition to the anatomical and functional disorganization of intrapituitary cell networks.
authors.affiliation: Department of Endocrinology and Metabolic Diseases (F.R., A.M.P., N.R.B.), Leiden University Medical Center, 2333ZA Leiden, The Netherlands; and Endocrine Research Unit (J.D.V.), Mayo Medical and Graduate Schools, Clinical Translational Research Center, Mayo Clinic, Rochester, Minnesota 55901.
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Roelfsema
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Pereira
authors.forename: Nienke R
authors.initials: NR
authors.lastname: Biermasz
authors.forename: Johannes D
authors.initials: JD
authors.lastname: Veldhuis
mesh_terms: D049913:ACTH-Secreting Pituitary Adenoma / Q000097:blood / Q000378:metabolism* / Q000601:surgery; D000172:Acromegaly / Q000378:metabolism / Q000601:surgery; D000236:Adenoma / Q000097:blood / Q000378:metabolism* / Q000601:surgery; D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism*; D000328:Adult; D000465:Algorithms; D019277:Entropy; D005260:Female; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000097:blood / Q000378:metabolism* / Q000601:surgery; D019382:Human Growth Hormone / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D047748:Pituitary ACTH Hypersecretion / Q000378:metabolism / Q000601:surgery; D015175:Prolactinoma / Q000097:blood / Q000378:metabolism / Q000601:surgery; D012720:Severity of Illness Index; D012737:Sex Factors; D013972:Thyrotropin / Q000097:blood / Q000378:metabolism*
chemical_list: D019382:Human Growth Hormone; D000324:Adrenocorticotropic Hormone; D013972:Thyrotropin