Ferdinand Roelfsema1, Alberto M Pereira, Nienke R Biermasz, Johannes D Veldhuis. 1. 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.
Abstract
CONTEXT: 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. CONCLUSION: 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.
CONTEXT: 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 acromegalicpatients 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 prolactinomapatients. CONCLUSION: 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: Johannes D Veldhuis; Ali Iranmanesh; Ferdinand Roelfsema; Paul Aoun; Paul Takahashi; John M Miles; Daniel M Keenan Journal: J Clin Endocrinol Metab Date: 2011-07-13 Impact factor: 5.958
Authors: Ferdinand Roelfsema; Simon Kok; Petra Kok; Alberto M Pereira; Nienke R Biermasz; Jan W Smit; Marijke Frolich; Daniel M Keenan; Johannes D Veldhuis; Johannes A Romijn Journal: Pituitary Date: 2009 Impact factor: 4.107
Authors: Peter Y Liu; Daniel M Keenan; Petra Kok; Vasantha Padmanabhan; Kevin T O'Byrne; Johannes D Veldhuis Journal: Am J Physiol Endocrinol Metab Date: 2009-06-16 Impact factor: 4.310
Authors: Johannes D Veldhuis; Ferdinand Roelfsema; Ali Iranmanesh; Bernard J Carroll; Daniel M Keenan; Steven M Pincus Journal: J Clin Endocrinol Metab Date: 2009-09-15 Impact factor: 5.958