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Horm Metab Res 2010; 42(1): 50-55
DOI: 10.1055/s-0029-1239522
Humans, Clinical

© Georg Thieme Verlag KG Stuttgart · New York

Discordant Nadir GH After Oral Glucose and IGF-I Levels on Treated Acromegaly: Refining the Biochemical Markers of Mild Disease Activity

P. C. L. Elias1 , H. B. Lugao1 , M. C. Pereira1 , H. R. Machado2 , M. de Castro1 , A. C. Moreira1
  • 1Division of Endocrinology and School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
  • 2Division of Neurosurgery, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
Further Information

Publication History

received 07.07.2009

accepted 26.08.2009

Publication Date:
01 October 2009 (online)

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Abstract

Biochemical markers for remission on acromegaly activity are controversial. We studied a subset of treated acromegalic patients with discordant nadir GH levels after oral glucose tolerance test (oGTT) and IGF-I values to refine the current consensus on acromegaly remission. We also compared GH results by two GH immunoassays. From a cohort of 75 treated acromegalic patients, we studied 13 patients who presented an elevated IGF-I despite post-oGTT nadir GH of ≤1 μg/l. The 12-h daytime GH profile (GH-12 h), nadir GH after oGTT, and basal IGF-I levels were studied in patients and controls. Bland-Altman method showed high concordance between GH assays. Acromegalic patients showed higher mean GH-12 h values (0.71±0.36 vs. 0.31±0.28 μg/l; p<0.05) and nadir GH after oGTT (0.48±0.32 vs. 0.097±0.002 μg/l; p<0.05) as compared to controls. Nadir GH correlated with mean GH-12 h (r=0.92, p<0.05). The mean GH-12 h value from upper 95% CI of controls (0.54 μg/l) would correspond to a theoretical normal nadir GH of ≤0.27 μg/l. Patients with GH nadir ≤0.3 μg/l had IGF-I between 100–130% ULNR (percentage of upper limit of normal range) and mean GH-12 h of 0.35±0.15, and patients with GH nadir >0.3 and ≤1 μg/l had IGF-I >130% ULNR and mean GH-12 h of 0.93±0.24 μg/l. Our data integrate daytime GH secretion, nadir GH after oGTT, and plasma IGF-I concentrations showing a continuum of mild residual activity in a subgroup of treated acromegaly with nadir GH values ≤1 μg/l. The degree of increased IGF-I levels and nadir GH after oGTT are correlated with the subtle abnormalities of daytime GH secretion.

Key words

acromegaly - GH - IGF-I

References

  • 1 Ben-Shlomo A, Melmed S. Acromegaly.  Endocrinol Metab Clin North Am. 2008;  37 101-122
    Google Scholar
  • 2 Chanson P, Salenave S. Acromegaly.  Orphanet J Rare Dis. 2008;  3 17
    Google Scholar
  • 3 Clemmons DR, Strasburger C. Monitoring the response to treatment in acromegaly.  J Clin Endocrinol Metab. 2004;  89 5289-5291
    Google Scholar
  • 4 Wood P. Growth hormone: Its measurement and the need for assay harmonization.  Ann Clin Biochem. 2001;  38 471-482
    Google Scholar
  • 5 Bidlingmaier M, Strasburger CJ. Growth hormone assays: Current methodologies and their limitations.  Pituitary. 2007;  10 115-119
    Google Scholar
  • 6 Trainer PJ, Barth J, Sturgeon C, Wieringaon G. Consensus statement on the standardisation of GH assays.  Eur J Endocrinol. 2006;  155 1-2
    Google Scholar
  • 7 Giustina A, Barkan A, Casanueva FF, Cavagnini F, Frohman L, Ho K, Veldhuis J, Wass J, Von Werder K, Melmed S. Criteria for cure of acromegaly: A consensus statement.  J Clin Endocrinol Metab. 2000;  85 526-529
    Google Scholar
  • 8 Freda PU, Post KD, Powell JS, Wardlaw SL. Evaluation of disease status with sensitive measures of growth hormone secretion in 60 postoperative patients with acromegaly.  J Clin Endocrinol Metab. 1998;  83 3808-3816
    Google Scholar
  • 9 Costa AC, Rossi A, Martinelli CE, Machado HR, Moreira AC. Assessment of disease activity in treated acromegalic patients using a sensitive GH assay: Should we achieve strict normal GH levels for a biochemical cure?.  J Clin Endocrinol Metab. 2002;  87 3142-3147
    Google Scholar
  • 10 Gullu S, Keles H, Delibasi T, Tonyukuk V, Kamel N, Erdogan G. Remission criteria for the follow-up of patients with acromegaly.  Eur J Endocrinol. 2004;  150 465-471
    Google Scholar
  • 11 Trainer PJ. Editorial: Acromegaly – consensus, what consensus?.  J Clin Endocrinol Metab. 2002;  87 3534-3536
    Google Scholar
  • 12 Freda PU. Current concepts in the biochemical assessment of the patient with acromegaly.  Growth Horm IGF Res. 2003;  13 171-184
    Google Scholar
  • 13 Melmed S, Casanueva FF, Cavagnini F, Chanson P, Frohman L, Grossman A, Ho K, Kleinberg D, Lamberts S, Laws E, Lombardi G, Vance ML, Werder KV, Wass J, Giustina A. Guidelines for acromegaly management.  J Clin Endocrinol Metab. 2002;  87 4054-4058
    Google Scholar
  • 14 Melmed S, Colao A, Barkan A, Molitch M, Grossman AB, Kleinberg D, Clemmons D, Chanson P, Laws E, Schlechte J, Vance ML, Ho K, Giustina A. Guidelines for acromegaly management: An update.  J Clin Endocrinol Metab. 2009;  94 1509-1517
    Google Scholar
  • 15 Vierhapper H, Heinze G, Gessl A, Exner M, Bieglmayr C. Use of the oral glucose tolerance test to define remission in acromegaly.  Metabolism. 2003;  52 181-185
    Google Scholar
  • 16 Puder JJ, Nilavar S, Post KD, Freda PU. Relationship between disease-related morbidity and biochemical markers of activity in patients with acromegaly.  J Clin Endocrinol Metab. 2005;  90 1972-1978
    Google Scholar
  • 17 Vieira JG, Ando MH, Nishida SK, Macedo CD, Abucham JZ. Clinical utility of a 22-kda growth hormone-specific assay.  Braz J Med Biol Res. 1992;  25 243-245
    Google Scholar
  • 18 Bland JM, Altman DG. Measuring agreement in method comparison studies.  Stat Methods Med Res. 1999;  8 135-160
    Google Scholar
  • 19 Lin LI. A concordance correlation coefficient to evaluate reproducibility.  Biometrics. 1989;  45 255-268
    Google Scholar
  • 20 Ho KY, Weissberger AJ. Characterization of 24-h growth hormone secretion in acromegaly: Implications for diagnosis and therapy.  Clin Endocrinol (Oxf). 1994;  41 75-83
    Google Scholar
  • 21 Kaltsas GA, Isidori AM, Florakis D, Trainer PJ, Camacho-Hubner C, Afshar F, Sabin I, Jenkins JP, Chew SL, Monson JP, Besser GM, Grossman AB. Predictors of the outcome of surgical treatment in acromegaly and the value of the mean growth hormone day curve in assessing postoperative disease activity.  J Clin Endocrinol Metab. 2001;  86 1645-1652
    Google Scholar
  • 22 Arafat AM, Mohlig M, Weickert MO, Perschel FH, Purschwitz J, Spranger J, Strasburger CJ, Schofl C, Pfeiffer AF. Growth hormone response during oGTT: The impact of assay method on the estimation of reference values in patients with acromegaly and in healthy controls and the role of gender, age, and BMI.  J Clin Endocrinol Metab. 2008;  93 1254-1262
    Google Scholar
  • 23 Espinosa-de-Los-Monteros AL, Sosa E, Cheng S, Ochoa R, Sandoval C, Guinto G, Mendoza V, Hernandez I, Molina M, Mercado M. Biochemical evaluation of disease activity after pituitary surgery in acromegaly: A critical analysis of patients who spontaneously change disease status.  Clin Endocrinol (Oxf). 2006;  64 245-249
    Google Scholar
  • 24 Carmichael JD, Bonert VS, Mirocha JM, Melmed S. The utility of oral glucose tolerance testing for diagnosis and assessment of treatment outcomes in 166 patients with acromegaly.  J Clin Endocrinol Metab. 2008;  94 523-527
    Google Scholar
  • 25 Semer M, Faria AC, Nery M, Salgado LR, Knoepfelmacher M, Wajchenberg BL, Liberman B. Growth hormone pulsatility in active and cured acromegalic subjects.  J Clin Endocrinol Metab. 1995;  80 3767-3770
    Google Scholar
  • 26 van den Berg G, Veldhuis JD, Frolich M, Roelfsema F. An amplitude-specific divergence in the pulsatile mode of growth hormone (GH) secretion underlies the gender difference in mean GH concentrations in men and premenopausal women.  J Clin Endocrinol Metab. 1996;  81 2460-2467
    Google Scholar
  • 27 Freda PU, Nuruzzaman AT, Reyes CM, Sundeen RE, Post KD. Significance of “Abnormal” nadir growth hormone levels after oral glucose in postoperative patients with acromegaly in remission with normal insulin-like growth factor-I levels.  J Clin Endocrinol Metab. 2004;  89 495-500
    Google Scholar
  • 28 Sherlock M, Aragon Alonso A, Reulen RC, Ayuk J, Clayton RN, Holder G, Sheppard MC, Bates A, Stewart PM. Monitoring disease activity using growth hormone and insulin like growth factor-I in the follow up of 501 patients with acromegaly.  Clin Endocrinol. 2008;  71 74-81
    Google Scholar
  • 29 Colao A, Pivonello R, Cavallo LM, Gaccione M, Auriemma RS, Esposito F, Cappabianca P, Lombardi G. Age changes the diagnostic accuracy of mean profile and nadir growth hormone levels after oral glucose in postoperative patients with acromegaly.  Clin Endocrinol (Oxf). 2006;  65 250-256
    Google Scholar
  • 30 Peacey SR, Toogood AA, Veldhuis JD, Thorner MO, Shalet SM. The relationship between 24-h growth hormone secretion and insulin-like growth factor I in patients with successfully treated acromegaly: Impact of surgery or radiotherapy.  J Clin Endocrinol Metab. 2001;  86 259-266
    Google Scholar
  • 31 Dimaraki EV, Jaffe CA, DeMott-Friberg R, Chandler WF, Barkan AL. Acromegaly with apparently normal GH secretion: Implications for diagnosis and follow-up.  J Clin Endocrinol Metab. 2002;  87 3537-3542
    Google Scholar
  • 32 Melmed S, Casanueva F, Cavagnini F, Chanson P, Frohman LA, Gaillard R, Ghigo E, Ho K, Jaquet P, Kleinberg D, Lamberts S, Laws E, Lombardi G, Sheppard MC, Thorner M, Vance ML, Wass JA, Giustina A. Consensus statement: Medical management of acromegaly.  Eur J Endocrinol. 2005;  153 737-740
    Google Scholar
  • 33 Ayuk J, Sheppard MC. Does acromegaly enhance mortality?.  Rev Endocr Metab Disord. 2008;  9 33-39
    Google Scholar
  • 34 Holdaway IM, Bolland MJ, Gamble GD. A meta-analysis of the effect of lowering serum levels of GH and IGF-I on mortality in acromegaly.  Eur J Endocrinol. 2008;  159 89-95
    Google Scholar
  • 35 Bajuk Studen K, Barkan A. Assessment of the magnitude of growth hormone hypersecretion in active acromegaly: Reliability of different sampling models.  J Clin Endocrinol Metab. 2008;  93 491-496
    Google Scholar

Correspondence

P. C. L. Elias

Department of Medicine School of Medicine of Ribeirão Preto University of São Paulo

14049-900 Ribeirão Preto

Brazil

Phone: +55/16/3602 29 37

Fax: +55/16/3633 66 95

Email: lamparelli@hotmail.com