title: Complex rhythmicity and age dependence of growth hormone secretion are preserved in patients with acromegaly: further evidence for a present hypothalamic control of pituitary somatotropinomas.
abstract: BACKGROUND
  Traditionally, acromegaly is viewed as a disease resulting from GH hypersecretion from an autonomous pituitary somatotropinoma.
  
  
  OBJECTIVE
  To test the hypothesis that GH secretion in acromegaly is still subjected to normal hypothalamic control, we studied the daily rhythmicity of GH secretion in normal controls and patients with newly diagnosed, untreated acromegaly.
  
  
  METHODS
  This was an observational inpatient study in the General Clinical Research Center at the University of Michigan.
  
  
  METHODS
  One hundred four normal controls and 67 acromegalic patients were included in the study.
  
  
  METHODS
  The intervention consisted of frequent blood sampling over 24 hours.
  
  
  METHODS
  We hypothesized that acromegalic patients would show rhythmicity, sexual dimorphism, and age-related decline of GH secretion similar to normal controls.
  
  
  RESULTS
  Both normal controls and the patients exhibited 3 major GH waves with the highest values at 12:00 pm, 5:00 pm, and 1:00 am (P < .001 for all). Both controls and patients exhibited a clear appearance of the nocturnal GH waves, irrespective of the gender (P < .001 for all). The amplitude of the maximal (nocturnal) GH secretory wave (1:00 am) as compared with the nadir GH secretion (9:00 am) was clearly different between the 2 groups, with a significantly smaller magnitude in acromegaly (P < .001). A subsequent subanalysis of both groups was performed separately for both genders. Similar to the entire groups, both controls and patients exhibited a clear appearance of the nocturnal GH waves, irrespective of the gender (P < .001 for all). Patients with clearly elevated GH values have shown an age-related decline of GH secretion (r = -0.35, P < .001), similar to controls.
  
  
  CONCLUSIONS
  The analysis of GH profiles in multiple patients with untreated acromegaly discloses the persistence of the hallmarks of the central control of GH regulation, ie, nictohemeral rhythmicity, sexual dimorphism, and an age-related decline of GH output.
authors: Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
authors: Antônio
authors: A
authors: Ribeiro-Oliveira
authors: Marcelo Militão
authors: MM
authors: Abrantes
authors: Ariel L
authors: AL
authors: Barkan
mesh_terms: D000172:Acromegaly / Q000097:blood / Q000503:physiopathology*; D000328:Adult; D000368:Aged; D000375:Aging; D002940:Circadian Rhythm; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D015536:Down-Regulation; D005260:Female; D019382:Human Growth Hormone / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000503:physiopathology*; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012727:Sex Characteristics; D055815:Young Adult
chemical_list: D019382:Human Growth Hormone
references: Endocr Rev. 1993 Feb;14(1):20-39
references: 8491152
references: J Clin Endocrinol Metab. 2008 May;93(5):1988-94
references: 18334589
references: Eur J Endocrinol. 2011 Jan;164(1):17-22
references: 20926592
references: Endocrinology. 1991 Oct;129(4):1791-6
references: 1915068
references: Pituitary. 2006;9(2):121-5
references: 16845601
references: J Gerontol A Biol Sci Med Sci. 2001 Feb;56(2):M124-9
references: 11213276
references: Am J Physiol Endocrinol Metab. 2002 Nov;283(5):E1008-15
references: 12376329
references: J Clin Endocrinol Metab. 1999 Jun;84(6):2140-50
references: 10372723
references: J Clin Endocrinol Metab. 2002 Aug;87(8):3537-42
references: 12161471
references: Horm Res. 1995;43(1-3):39-45
references: 7721260
references: Growth Horm IGF Res. 2005 Apr;15(2):95-122
references: 15809014
references: Endocrinology. 1991 Jun;128(6):2858-66
references: 1674685
references: Proc Natl Acad Sci U S A. 2006 Jan 10;103(2):413-8
references: 16381821
references: J Clin Endocrinol Metab. 2001 Nov;86(11):5554-63
references: 11701735
references: Exp Clin Endocrinol Diabetes. 1996;104(2):145-50
references: 8740938
references: Science. 1985 Oct 25;230(4724):461-3
references: 2864742
references: Endocrinology. 1988 Dec;123(6):2605-10
references: 3197637
references: J Clin Endocrinol Metab. 2006 Jun;91(6):2185-90
references: 16537684
references: Mol Cell Endocrinol. 2012 Feb 5;349(1):91-104
references: 21939733
references: Am J Physiol Regul Integr Comp Physiol. 2005 Jul;289(1):R125-33
references: 15746304
references: J Clin Endocrinol Metab. 1989 Dec;69(6):1225-33
references: 2511221
references: J Clin Endocrinol Metab. 2008 May;93(5):1526-40
references: 18334580
references: J Clin Endocrinol Metab. 2003 Oct;88(10):4776-80
references: 14557454
references: J Endocrinol Invest. 1999;22(5 Suppl):22-6
references: 10442566
references: J Clin Invest. 1998 Jul 1;102(1):153-64
references: 9649569
references: J Biol Regul Homeost Agents. 2011 Apr-Jun;25(2):231-8
references: 21880212
references: J Clin Endocrinol Metab. 2001 Sep;86(9):4364-70
references: 11549676
references: J Clin Endocrinol Metab. 1996 May;81(5):1798-805
references: 8626838
references: Mol Pharmacol. 2009 Aug;76(2):215-28
references: 19483103
references: J Clin Endocrinol Metab. 1993 May;76(5):1363-8
references: 8496331
references: Eur J Endocrinol. 2008 Oct;159(4):375-9
references: 18653547
references: J Clin Endocrinol Metab. 1999 Oct;84(10):3490-7
references: 10522985
references: FASEB J. 1992 Jan 6;6(2):711-8
references: 1537461