Reduced disorderliness of growth hormone release in biochemically inactive acromegaly after pituitary surgery

Department of Endocrinology, Leiden University Medical Center, The Netherlands.

The episodicity of 24 h GH release was studied in 18 patients with active acromegaly, 12 patients 7-10 days after pituitary surgery, 14 patients long after operation (3-17 years), and 21 healthy gender- and age-matched control subjects, using a recently introduced scale- and model-independent regularity statistic, approximate entropy (ApEn). Blood samples were taken at 10-min intervals for 24 h, and plasma GH concentrations were measured by immunofluorometric assay (detection limit 11.5 ng/l). For this study we selected operated patients who were biochemically in remission, defined by normal circulating IGF-I and insulin-like growth factor-binding protein-3 (IGFBP-3) concentrations, normal glucose-suppressed plasma GH concentration (<0.38 microg/l), and the normalization of the paradoxical rise of GH to TRH or GnRH. In patients with active acromegaly ApEn was 1.23+/-0.04, with no overlap with the control subjects (P = 1.2 x 10[-16]), who had an ApEn of 0.40+/-0.04. ApEn in patients shortly after surgery was 0.71+/-0.09 (P < 0.001 vs controls), and long after surgery 0.56+/-0.05 (P < 0.011 vs controls). ApEn values in treated and untreated patients correlated significantly with the plasma concentration of IGF-I (r=0.531) and IGFBP-3 (r=0.598), and the log-transformed 24h GH secretion rate (r=0.749). Shortly after surgery only one-third of the patients had a normal ApEn value, whereas long after surgery about 70% of the patients had a normal ApEn value. Although ApEn eventually normalized in about 70% of the operated patients, the cause of the persistence of abnormal GH release in the remainder of the subjects is not known, and might reflect permanent hypothalamic-pituitary dysfunction or a very early recurrence of the somatotroph adenoma.

This article has been cited by other articles:

				A A van der Klaauw, A M Pereira, S W van Thiel, J W A Smit, E P M Corssmit, N R Biermasz, M Frolich, A Iranmanesh, J D Veldhuis, F Roelfsema, et al. GH deficiency in patients irradiated for acromegaly: significance of GH stimulatory tests in relation to the 24 h GH secretion. Eur. J. Endocrinol., June 1, 2006; 154(6): 851 - 858. [Abstract] [Full Text] [PDF]

				K. H. Darzy, S. S. Pezzoli, M. O. Thorner, and S. M. Shalet The Dynamics of Growth Hormone (GH) Secretion in Adult Cancer Survivors with Severe GH Deficiency Acquired after Brain Irradiation in Childhood for Nonpituitary Brain Tumors: Evidence for Preserved Pulsatility and Diurnal Variation with Increased Secretory Disorderliness J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2794 - 2803. [Abstract] [Full Text] [PDF]

				N. R. Biermasz, A. M. Pereira, J. W. A. Smit, J. A. Romijn, and F. Roelfsema Morbidity after Long-Term Remission for Acromegaly: Persisting Joint-Related Complaints Cause Reduced Quality of Life J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2731 - 2739. [Abstract] [Full Text] [PDF]

				M. O. van Aken, A. M. Pereira, M. Frolich, J. A. Romijn, H. Pijl, J. D. Veldhuis, and F. Roelfsema Growth hormone secretion in primary adrenal Cushing's syndrome is disorderly and inversely correlated with body mass index Am J Physiol Endocrinol Metab, January 1, 2005; 288(1): E63 - E70. [Abstract] [Full Text] [PDF]

				N. R. Biermasz, A. M. Pereira, M. Frolich, J. A. Romijn, J. D. Veldhuis, and F. Roelfsema Octreotide represses secretory-burst mass and nonpulsatile secretion but does not restore event frequency or orderly GH secretion in acromegaly Am J Physiol Endocrinol Metab, January 1, 2004; 286(1): E25 - E30. [Abstract] [Full Text]

				J. Svensson, J. D. Veldhuis, A. Iranmanesh, B.-A. Bengtsson, and G. Johannsson Increased Orderliness of Growth Hormone (GH) Secretion in GH-Deficient Adults with Low Serum Insulin-Like Growth Factor I J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2863 - 2869. [Abstract] [Full Text] [PDF]

				J. D. Veldhuis, M. L. Johnson, O. L. Veldhuis, M. Straume, and S. M. Pincus Impact of pulsatility on the ensemble orderliness (approximate entropy) of neurohormone secretion Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2001; 281(6): R1975 - R1985. [Abstract] [Full Text] [PDF]

				F. Roelfsema, N. R. Biermasz, R. G. Veldman, J. D. Veldhuis, M. Frolich, W. H. Stokvis-Brantsma, and J.-M. Wit Growth Hormone (GH) Secretion in Patients with an Inactivating Defect of the GH-Releasing Hormone (GHRH) Receptor Is Pulsatile: Evidence for a Role for Non-GHRH Inputs into the Generation of GH Pulses J. Clin. Endocrinol. Metab., June 1, 2001; 86(6): 2459 - 2464. [Abstract] [Full Text] [PDF]

				S. R. Peacey, A. A. Toogood, J. D. Veldhuis, M. O. Thorner, and S. M. Shalet The Relationship between 24-Hour Growth Hormone Secretion and Insulin-Like Growth Factor I in Patients with Successfully Treated Acromegaly: Impact of Surgery or Radiotherapy J. Clin. Endocrinol. Metab., January 1, 2001; 86(1): 259 - 266. [Abstract] [Full Text]

				N. R. Biermasz, H. van Dulken, and F. Roelfsema Ten-Year Follow-Up Results of Transsphenoidal Microsurgery in Acromegaly J. Clin. Endocrinol. Metab., December 1, 2000; 85(12): 4596 - 4602. [Abstract] [Full Text]

				R. G. Veldman, M. Frölich, S. M. Pincus, J. D. Veldhuis, and F. Roelfsema Apparently Complete Restoration of Normal Daily Adrenocorticotropin, Cortisol, Growth Hormone, and Prolactin Secretory Dynamics in Adults with Cushing's Disease after Clinically Successful Transsphenoidal Adenomectomy J. Clin. Endocrinol. Metab., November 1, 2000; 85(11): 4039 - 4046. [Abstract] [Full Text]

				J. D. Veldhuis, Ali Iranmanesh, Thomas Mulligan, and Steven M. Pincus Disruption of the Young-Adult Synchrony between Luteinizing Hormone Release and Oscillations in Follicle-Stimulating Hormone, Prolactin, and Nocturnal Penile Tumescence (NPT) in Healthy Older Men J. Clin. Endocrinol. Metab., October 1, 1999; 84(10): 3498 - 3505. [Abstract] [Full Text] [PDF]

				H. Olivecrona, A. Hilding, C. Ekström, H. Barle, B. Nyberg, C. Möller, P. J. Delhanty, R. C. Baxter, B. Angelin, T. J. Ekström, et al. Acute and Short-Term Effects of Growth Hormone on Insulin-Like Growth Factors and Their Binding Proteins: Serum Levels and Hepatic Messenger Ribonucleic Acid Responses in Humans J. Clin. Endocrinol. Metab., February 1, 1999; 84(2): 553 - 560. [Abstract] [Full Text]

				A. Giustina and J. D. Veldhuis Pathophysiology of the Neuroregulation of Growth Hormone Secretion in Experimental Animals and the Human Endocr. Rev., December 1, 1998; 19(6): 717 - 797. [Abstract] [Full Text]