Advertisement

Endocrine

pp 1–8 | Cite as

Is GH nadir during OGTT a reliable test for diagnosis of acromegaly in patients with abnormal glucose metabolism?

  • Georgiana Dobri
  • Soamsiri Niwattisaiwong
  • James F. Bena
  • Manjula Gupta
  • John Kirwan
  • Lawrence Kennedy
  • Amir H. Hamrahian
Original Article
  • 28 Downloads

Abstract

Purpose

The growth hormone (GH) nadir during oral glucose tolerance test (OGTT) is the gold standard diagnostic test for acromegaly. The utility of OGTT-GH suppression test in patients with abnormal glucose metabolism (AGM) has not been well established. In this study, we compared the GH nadir during OGTT in patients evaluated for acromegaly in the presence and absence of AGM.

Methods

This is a retrospective cohort study of patients with acromegaly (G1, n = 40) and a group in whom acromegaly was not confirmed (G2, n = 53) who had OGTT-GH suppression test during 2000–2012, using a monoclonal GH immunoenzymatic assay. The patients were categorized as having normal glucose metabolism (NGM) or AGM. GH nadir during OGTT in each group were compared.

Results

In G1 and G2, 17 and 19 patients had AGM, respectively. Among 17 patients with diabetes, median HbA1C was 7% (range 5.7–9.6%). All except one patient had HbA1C< 8%. There was no difference in the GH nadir in patients with or without AGM within G1 (p = 0.15) and G2 (p = 0.43). All G1 patients with AGM had GH nadir > 0.4 µg/L. Four G1 patients with NGM had GH nadir<0.4 µg/L. All G2 patients had GH nadir < 0.4 µg/L, except one with NGM and GH nadir of 0.4 µg/L.

Conclusion

Using highly sensitive GH assay, a GH nadir ≥ 0.4 µg/L during the OGTT-GH suppression test may be used for diagnosis of acromegaly in patients with AGM in the absence of poorly controlled diabetes.

Keywords

Growth hormone nadir Acromegaly Diagnosis OGTT Diabetes 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethicall approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

References

  1. 1.
    S.K. Subbarayan, M. Fleseriu, M.B. Gordon, J.A. Brzana, L. Kennedy, C. Faiman, B.A. Hatipoglu, R.A. Prayson, J.B. Delashaw, R.J. Weil, A.H. Hamrahian, Serum IGF-1 in the diagnosis of acromegaly and the profile of patients with elevated IGF-1 but normal glucose-suppressed growth hormone. Endocr. Pract. 18(6), 817–825 (2012).  https://doi.org/10.4158/EP11324.OR CrossRefPubMedGoogle Scholar
  2. 2.
    L. Katznelson, E.R. Laws Jr., S. Melmed, M.E. Molitch, M.H. Murad, A. Utz, J.A. Wass, S. Endocrine, Acromegaly: an endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 99(11), 3933–3951 (2014).  https://doi.org/10.1210/jc.2014-2700 CrossRefPubMedGoogle Scholar
  3. 3.
    P.U. Freda, C.M. Reyes, A.T. Nuruzzaman, R.E. Sundeen, J.N. Bruce, Basal and glucose-suppressed GH levels less than 1 microg/L in newly diagnosed acromegaly. Pituitary 6(4), 175–180 (2003)CrossRefGoogle Scholar
  4. 4.
    E. Duncan, J.A. Wass, Investigation protocol: acromegaly and its investigation. Clin. Endocrinol. 50(3), 285–293 (1999)CrossRefGoogle Scholar
  5. 5.
    P.U. Freda, Pitfalls in the biochemical assessment of acromegaly. Pituitary 6(3), 135–140 (2003)CrossRefGoogle Scholar
  6. 6.
    P.H. Sonksen, J.S. Soeldner, R.E. Gleason, G. Boden, Abnormal serum growth hormone responses in genetically potential-diabetic male patients with normal oral glucose tolerance: evidence for an insulin-like action of growth hormone in vivo. Diabetologia 9(5), 426–437 (1973)CrossRefGoogle Scholar
  7. 7.
    E.O. Grecu, R.M. Walter Jr., E.M. Gold, Paradoxical release of growth hormone during oral glucose tolerance test in patients with abnormal glucose tolerance. Metabolism 32(2), 134–137 (1983)CrossRefGoogle Scholar
  8. 8.
    W.M. Hunter, B.F. Clarke, L.J. Duncan, Plasma growth hormone after an overnight fast and following glucose loading in healthy and diabetic subjects. Metabolism 15(7), 596–607 (1966)CrossRefGoogle Scholar
  9. 9.
    A. Bereket, C.H. Lang, S.L. Blethen, M.C. Gelato, J. Fan, R.A. Frost, T.A. Wilson, Effect of insulin on the insulin-like growth factor system in children with new-onset insulin-dependent diabetes mellitus. J. Clin. Endocrinol. Metab. 80(4), 1312–1317 (1995).  https://doi.org/10.1210/jcem.80.4.7536205 CrossRefPubMedGoogle Scholar
  10. 10.
    K.L. Clayton, J.M. Holly, L.M. Carlsson, J. Jones, T.D. Cheetham, A.M. Taylor, D.B. Dunger, Loss of the normal relationships between growth hormone, growth hormone-binding protein and insulin-like growth factor-I in adolescents with insulin-dependent diabetes mellitus. Clin. Endocrinol. (Oxf.). 41(4), 517–524 (1994)CrossRefGoogle Scholar
  11. 11.
    M. Maes, L.E. Underwood, J.M. Ketelslegers, Low serum somatomedin-C in insulin-dependent diabetes: evidence for a postreceptor mechanism. Endocrinology 118(1), 377–382 (1986).  https://doi.org/10.1210/endo-118-1-377 CrossRefPubMedGoogle Scholar
  12. 12.
    R.C. Baxter, J.M. Bryson, J.R. Turtle, Somatogenic receptors of rat liver: regulation by insulin. Endocrinology 107(4), 1176–1181 (1980).  https://doi.org/10.1210/endo-107-4-1176 CrossRefPubMedGoogle Scholar
  13. 13.
    P. Fainstein Day, J.A. Fagin, R.M. Vaglio, L.E. Litwak, M.F. Picasso, R.A. Gutman, Growth hormone-insulin-like growth factor-I axis in adult insulin-dependent diabetic patients: evidence for central hypersensitivity to growth hormone-releasing hormone and peripheral resistance to growth hormone. Horm. Metab. Res. 30(12), 737–742 (1998)CrossRefGoogle Scholar
  14. 14.
    H. Hanaire-Broutin, B. Sallerin-Caute, M.F. Poncet, M. Tauber, R. Bastide, J.J. Chale, R. Rosenfeld, J.P. Tauber, Effect of intraperitoneal insulin delivery on growth hormone binding protein, insulin-like growth factor (IGF)-I, and IGF-binding protein-3 in IDDM. Diabetologia 39(12), 1498–1504 (1996)CrossRefGoogle Scholar
  15. 15.
    C.M. Asplin, A.C. Faria, E.C. Carlsen, V.A. Vaccaro, R.E. Barr, A. Iranmanesh, M.M. Lee, J.D. Veldhuis, W.S. Evans, Alterations in the pulsatile mode of growth hormone release in men and women with insulin-dependent diabetes mellitus. J. Clin. Endocrinol. Metab. 69(2), 239–245 (1989).  https://doi.org/10.1210/jcem-69-2-239 CrossRefPubMedGoogle Scholar
  16. 16.
    N. Friedrich, B. Thuesen, T. Jorgensen, A. Juul, C. Spielhagen, H. Wallaschofksi, A. Linneberg, The association between IGF-I and insulin resistance: a general population study in Danish adults. Diabetes Care 35(4), 768–773 (2012).  https://doi.org/10.2337/dc11-1833 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    D.R. Clemmons, Metabolic actions of insulin-like growth factor-I in normal physiology and diabetes. Endocrinol. Metab. Clin. North. Am. 41(2), 425–443 (2012).  https://doi.org/10.1016/j.ecl.2012.04.017. vii-viiiCrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    C.H. Anderwald, A. Tura, A. Gessl, S. Smajis, C. Bieglmayer, R. Marculescu, A. Luger, G. Pacini, M. Krebs, Whole-body insulin sensitivity rather than body-mass-index determines fasting and post-glucose-load growth hormone concentrations. PLoS ONE 9(12), e115184 (2014).  https://doi.org/10.1371/journal.pone.0115184 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    A. Giustina, J.D. Veldhuis, Pathophysiology of the neuroregulation of growth hormone secretion in experimental animals and the human. Endocr. Rev. 19(6), 717–797 (1998).  https://doi.org/10.1210/edrv.19.6.0353 CrossRefPubMedGoogle Scholar
  20. 20.
    N. Hattori, A. Shimatsu, Y. Kato, H. Koshiyama, Y. Ishikawa, H. Assadian, T. Tanoh, M. Nagao, H. Imura, Growth hormone responses to oral glucose loading measured by highly sensitive enzyme immunoassay in normal subjects and patients with glucose intolerance and acromegaly. J. Clin. Endocrinol. Metab. 70(3), 771–776 (1990).  https://doi.org/10.1210/jcem-70-3-771 CrossRefPubMedGoogle Scholar
  21. 21.
    M.J. Kayath, E.M. Russo, S.A. Dib, J.G. Vieira, Do impaired glucose tolerance and diabetes mellitus interfere with the interpretation of the growth hormone response to the oral glucose tolerance test? Braz. J. Med. Biol. Res. 25(5), 449–455 (1992)PubMedGoogle Scholar
  22. 22.
    P. Dutta, S. Singhal, N.K. Sachdeva, V.N. Shah, A. Pathak, K.K. Mukherjee, A. Bhansali, Diagnostic utility of serum GH, IGF-1 and IGFBP3 in patients of acromegaly with uncontrolled diabetes: a pilot study. J. Assoc. Physicians India 62(8), 686–690 (2014)PubMedGoogle Scholar
  23. 23.
    P.W. Rosario, M.R. Calsolari, Safety and specificity of the growth hormone suppression test in patients with diabetes. Endocrine 48(1), 329–333 (2015).  https://doi.org/10.1007/s12020-014-0282-2 CrossRefPubMedGoogle Scholar
  24. 24.
    E.V. Dimaraki, C.A. Jaffe, R. DeMott-Friberg, W.F. Chandler, A.L. Barkan, Acromegaly with apparently normal GH secretion: implications for diagnosis and follow-up. J. Clin. Endocrinol. Metab. 87(8), 3537–3542 (2002).  https://doi.org/10.1210/jcem.87.8.8658 CrossRefPubMedGoogle Scholar
  25. 25.
    L. Katznelson, J.L. Atkinson, D.M. Cook, S.Z. Ezzat, A.H. Hamrahian, K.K. Miller; American Association of Clinical, E., American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of acromegaly--2011 update. Endocr. Pract. 17, 1–44 (2011)CrossRefGoogle Scholar
  26. 26.
    S. Melmed, F. Casanueva, F. Cavagnini, P. Chanson, L.A. Frohman, R. Gaillard, E. Ghigo, K. Ho, P. Jaquet, D. Kleinberg, S. Lamberts, E. Laws, G. Lombardi, M.C. Sheppard, M. Thorner, M.L. Vance, J.A. Wass, A. Giustina, Consensus statement: medical management of acromegaly. Eur. J. Endocrinol. 153(6), 737–740 (2005).  https://doi.org/10.1530/eje.1.02036 CrossRefPubMedGoogle Scholar
  27. 27.
    A.M. Arafat, M. Mohlig, M.O. Weickert, F.H. Perschel, J. Purschwitz, J. Spranger, C.J. Strasburger, C. Schofl, A.F. Pfeiffer, Growth hormone response during oral glucose tolerance test: 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 body mass index. J. Clin. Endocrinol. Metab. 93(4), 1254–1262 (2008).  https://doi.org/10.1210/jc.2007-2084 CrossRefPubMedGoogle Scholar
  28. 28.
    I. Bancos, A. Algeciras-Schimnich, W.W. Woodmansee, A.K. Cullinane, L.J. Donato, T.B. Nippoldt, N. Natt, D. Erickson, Determination of nadir growth hormone concentration cutoff in patients with acromegaly. Endocr. Pract. 19(6), 937–945 (2013).  https://doi.org/10.4158/EP12435.OR CrossRefPubMedGoogle Scholar
  29. 29.
    A.T. Faje, A.L. Barkan, Basal, but not pulsatile, growth hormone secretion determines the ambient circulating levels of insulin-like growth factor-I. J. Clin. Endocrinol. Metab. 95(5), 2486–2491 (2010).  https://doi.org/10.1210/jc.2009-2634 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    A. Bereket, C.H. Lang, T.A. Wilson, Alterations in the growth hormone-insulin-like growth factor axis in insulin dependent diabetes mellitus. Horm. Metab. Res. 31(2-3), 172–181 (1999).  https://doi.org/10.1055/s-2007-978716 CrossRefPubMedGoogle Scholar
  31. 31.
    Z. Arihara, K. Sakurai, S. Yamada, O. Murakami, K. Takahashi, Acromegaly with normal IGF-1 levels probably due to poorly controlled diabetes mellitus. Tohoku J. Exp. Med. 216(4), 325–329 (2008)CrossRefGoogle Scholar
  32. 32.
    D.J. Lim, H.S. Kwon, J.H. Cho, S.H. Kim, Y.H. Choi, K.H. Yoon, B.Y. Cha, K.W. Lee, H.Y. Son, S.K. Kang, Acromegaly associated with type 2 diabetes showing normal IGF-1 levels under poorly controlled glycemia. Endocr. J. 54(4), 537–541 (2007)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Neurosurgery Weill Cornell MedicineNew YorkUSA
  2. 2.Division of EndocrinologyDiabetes and Metabolism Weill Cornell MedicineNew YorkUSA
  3. 3.Department of Endocrinology Sanford Health FargoNorth DakotaUSA
  4. 4.Department of Quantitative Health Sciences Cleveland ClinicClevelandUSA
  5. 5.Department of Laboratory MedicineCleveland ClinicClevelandUSA
  6. 6.Department of Integrated Physiology and Molecular MedicinePennington Biomedical Research CenterBaton RougeUSA
  7. 7.Department of EndocrinologyDiabetes and Metabolism Cleveland ClinicClevelandUSA
  8. 8.Division of EndocrinologyDiabetes and Metabolism Johns Hopkins UniversityBaltimoreUSA

Personalised recommendations