Skip to main content
SpringerLink
Log in

Can a glucagon stimulation test characterized by lower GH cut-off value be used for the diagnosis of growth hormone deficiency in adults?

  • Published:
Pituitary Aims and scope Submit manuscript

Abstract

Objective

The aim of this study was to assess diagnostic values of insulin tolerance test (ITT), glucagon stimulation test (GST), and insulin like growth factor-I (IGF-I) level, to find optimal GH cut-off values for GST, and to evaluate efficiencies of patient age, gender, body-mass index (BMI), and additional pituitary hormone deficiencies (PHDs) in the diagnosis of growth hormone deficiency (GHD).

Study design

This retrospective study involved 216 patients with a pituitary disease and 26 healthy controls. Age, gender, BMI, medical histories, and hormonal data including baseline and stimulated hormone values were evaluated. Three cut-off values for peak GH responses to stimulation tests were evaluated: (a) 3.00 µg/L on ITT, (b) 3.00 µg/L on GST, and (c) 1.07 µg/L on GST.

Results

According to the ITT, GST with 3.00 µg/L cut-off, and GST with 1.07 µg/L cut-off, GHD was present in 86.1, 74.5, and 54.2 % patients, respectively. Patient age, BMI, and number of PHDs, but not gender, were found to be correlated with IGF-I and peak GH concentrations. All patients with an IGF-I concentration ≤95 ng/ml or ≥3 PHD had GHD. None of the patients with adequate GH response to the GST with 1.07 µg/L cut-off, but blunted responses to ITT and GST with 3.00 µg/L cut-off, had ≥3 PHDs. 12 out of 26 (46.2 %) healthy subjects failed the GST with 3.00 µg/L cut-off, but not with 1.07 µg/L cut-off.

Conclusions

Patient age, IGF-I, BMI, and number of PHDs are efficient factors associated with the diagnosis of GHD. A 4 h GST with a diagnostic GH threshold of 1.07 µg/L seems to be a good diagnostic method for GHD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Carroll PV, Christ ER, Bengtsson BA, Carlsson L, Christiansen JS, Clemmons D, Hintz R, Ho K, Laron Z, Sizonenko P, Sonksen PH, Tanaka T, Thorne M (1998) Growth hormone deficiency in adulthood and the effects of growth hormone replacement: a review. Growth Hormone Research Society Scientific Committee. J Clin Endocrinol Metab 83(2):382–395. doi:10.1210/jcem.83.2.4594

    Article  CAS  PubMed  Google Scholar 

  2. de Boer H, Blok GJ, Van der Veen EA (1995) Clinical aspects of growth hormone deficiency in adults. Endocr Rev 16(1):63–86. doi:10.1210/edrv-16-1-63

    Article  PubMed  Google Scholar 

  3. Stochholm K, Christiansen J, Laursen T, Gravholt CH (2007) Mortality and reduced growth hormone secretion. Horm Res 68(Suppl 5):173–176. doi:10.1159/000110618

    Article  PubMed  Google Scholar 

  4. Mukherjee A, Shalet SM (2009) The value of IGF1 estimation in adults with GH deficiency. Eur J Endocrinol 161(Suppl 1):S33–S39. doi:10.1530/EJE-09-0247

    Article  CAS  PubMed  Google Scholar 

  5. Lissett CA, Jonsson P, Monson JP, Shalet SM (2003) Determinants of IGF-I status in a large cohort of growth hormone-deficient (GHD) subjects: the role of timing of onset of GHD. Clin Endocrinol (Oxf) 59(6):773–778. doi:10.1046/j.1365-2265.2003.01884.x

    Article  CAS  Google Scholar 

  6. Hoffman DM, O’Sullivan AJ, Baxter RC, Ho KK (1994) Diagnosis of growth-hormone deficiency in adults. Lancet 343(8905):1064–1068

    Article  CAS  PubMed  Google Scholar 

  7. Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Vance ML (2011) Evaluation and treatment of adult growth hormone deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 96(6):1587–1609. doi:10.1210/jc.2011-0179

    Article  CAS  PubMed  Google Scholar 

  8. Aimaretti G, Baffoni C, DiVito L, Bellone S, Grottoli S, Maccario M, Arvat E, Camanni F, Ghigo E (2000) Comparisons among old and new provocative tests of GH secretion in 178 normal adults. Eur J Endocrinol 142(4):347–352

    Article  CAS  PubMed  Google Scholar 

  9. Aimaretti G, Corneli G, Razzore P, Bellone S, Baffoni C, Arvat E, Camanni F, Ghigo E (1998) Comparison between insulin-induced hypoglycemia and growth hormone (GH)-releasing hormone + arginine as provocative tests for the diagnosis of GH deficiency in adults. J Clin Endocrinol Metab 83(5):1615–1618. doi:10.1210/jcem.83.5.4837

    CAS  PubMed  Google Scholar 

  10. Popovic V, Leal A, Micic D, Koppeschaar HP, Torres E, Paramo C, Obradovic S, Dieguez C, Casanueva FF (2000) GH-releasing hormone and GH-releasing peptide-6 for diagnostic testing in GH-deficient adults. Lancet 356(9236):1137–1142

    Article  CAS  PubMed  Google Scholar 

  11. Yuen KC, Biller BM, Molitch ME, Cook DM (2009) Clinical review: is lack of recombinant growth hormone (GH)-releasing hormone in the United States a setback or time to consider glucagon testing for adult GH deficiency? J Clin Endocrinol Metab 94(8):2702–2707. doi:10.1210/jc.2009-0299

    Article  CAS  PubMed  Google Scholar 

  12. Lee P, Greenfield JR, Ho KK (2009) Factors determining inadequate hypoglycaemia during insulin tolerance testing (ITT) after pituitary surgery. Clin Endocrinol (Oxf) 71(1):82–85. doi:10.1111/j.1365-2265.2008.03466.x

    Article  CAS  Google Scholar 

  13. Hoeck HC, Vestergaard P, Jakobsen PE, Laurberg P (1995) Test of growth hormone secretion in adults: poor reproducibility of the insulin tolerance test. Eur J Endocrinol 133(3):305–312

    Article  CAS  PubMed  Google Scholar 

  14. Casanueva FF, Villanueva L, Cabranes JA, Cabezas-Cerrato J, Fernandez-Cruz A (1984) Cholinergic mediation of growth hormone secretion elicited by arginine, clonidine, and physical exercise in man. J Clin Endocrinol Metab 59(3):526–530. doi:10.1210/jcem-59-3-526

    Article  CAS  PubMed  Google Scholar 

  15. Page MD, Dieguez C, Valcavi R, Edwards C, Hall R, Scanlon MF (1988) Growth hormone (GH) responses to arginine and l-dopa alone and after GHRH pretreatment. Clin Endocrinol (Oxf) 28(5):551–558

    Article  CAS  Google Scholar 

  16. Arosio M, Losa M, Bazzoni N, Bochicchio D, Palmieri E, Nava C, Faglia G (1990) Effects of propranolol on GH responsiveness to repeated GH-releasing hormone stimulations in normal subjects. Acta Endocrinol (Copenh) 122(6):735–739

    CAS  Google Scholar 

  17. Toogood A, Brabant G, Maiter D, Jonsson B, Feldt-Rasmussen U, Koltowska-Haggstrom M, Rasmussen AK, Buchfelder M, Saller B, Biller BM (2012) Similar clinical features among patients with severe adult growth hormone deficiency diagnosed with insulin tolerance test or arginine or glucagon stimulation tests. Endocr Pract 18(3):325–334. doi:10.4158/EP11146.OR

    Article  PubMed  Google Scholar 

  18. Micmacher E, Assumpcao RP, Redorat RG, Spina LD, Cruz IC, Silva CA, Vaisman M, Conceicao FL (2009) Growth hormone secretion in response to glucagon stimulation test in healthy middle-aged men. Arq Bras Endocrinol Metabol 53(7):853–858

    Article  PubMed  Google Scholar 

  19. Berg C, Meinel T, Lahner H, Yuece A, Mann K, Petersenn S (2010) Diagnostic utility of the glucagon stimulation test in comparison to the insulin tolerance test in patients following pituitary surgery. Eur J Endocrinol 162(3):477–482. doi:10.1530/EJE-09-0824

    Article  CAS  PubMed  Google Scholar 

  20. Gomez JM, Espadero RM, Escobar-Jimenez F, Hawkins F, Pico A, Herrera-Pombo JL, Vilardell E, Duran A, Mesa J, Faure E, Sanmarti A (2002) Growth hormone release after glucagon as a reliable test of growth hormone assessment in adults. Clin Endocrinol (Oxf) 56(3):329–334

    Article  CAS  Google Scholar 

  21. Leong KS, Walker AB, Martin I, Wile D, Wilding J, MacFarlane IA (2001) An audit of 500 subcutaneous glucagon stimulation tests to assess growth hormone and ACTH secretion in patients with hypothalamic-pituitary disease. Clin Endocrinol (Oxf) 54(4):463–468

    Article  CAS  Google Scholar 

  22. Rahim A, Toogood AA, Shalet SM (1996) The assessment of growth hormone status in normal young adult males using a variety of provocative agents. Clin Endocrinol (Oxf) 45(5):557–562

    Article  CAS  Google Scholar 

  23. Simsek Y, Karaca Z, Tanriverdi F, Unluhizarci K, Selcuklu A, Kelestimur F (2014) A comparison of low-dose ACTH, glucagon stimulation and insulin tolerance test in patients with pituitary disorders. Clin Endocrinol (Oxf). doi:10.1111/cen.12528

    Google Scholar 

  24. Dichtel LE, Yuen KC, Bredella MA, Gerweck AV, Russell BM, Riccio AD, Gurel MH, Sluss PM, Biller BM, Miller KK (2014) Overweight/obese adults with pituitary disorders require lower peak growth hormone cutoff values on glucagon stimulation testing to avoid overdiagnosis of growth hormone deficiency. J Clin Endocrinol Metab 99(12):4712–4719. doi:10.1210/jc.2014-2830

    Article  CAS  PubMed  Google Scholar 

  25. Satman I, Ozbey NC, Boztepe H, Telci A, Omer B, Tutuncu Y, Aral F, Alagol F (2013) Population-specific IGF levels and relationship between serum IGF1 and IGFBP3 levels, obesity, hypertension, diabetes and biochemical variables. Poster presented at The Endocrine Society's 95th Annual Meeting and Expo, San Francisco, 15–18 June 2013

  26. Tuchelt H, Dekker K, Bahr V, Oelkers W (2000) Dose-response relationship between plasma ACTH and serum cortisol in the insulin-hypoglycaemia test in 25 healthy subjects and 109 patients with pituitary disease. Clin Endocrinol (Oxf) 53(3):301–307

    Article  CAS  Google Scholar 

  27. Karaca Z, Lale A, Tanriverdi F, Kula M, Unluhizarci K, Kelestimur F (2011) The comparison of low and standard dose ACTH and glucagon stimulation tests in the evaluation of hypothalamo-pituitary-adrenal axis in healthy adults. Pituitary 14(2):134–140. doi:10.1007/s11102-010-0270-3

    Article  CAS  PubMed  Google Scholar 

  28. Mo D, Blum WF, Rosilio M, Webb SM, Qi R, Strasburger CJ (2014) Ten-year change in quality of life in adults on growth hormone (GH) replacement for GH deficiency: an analysis of the hypopituitary control and complications study (HypoCCS). J Clin Endocrinol Metab. doi:10.1210/jc.2014-2892

    PubMed  Google Scholar 

  29. Tanriverdi F, Karaca Z, Unluhizarci K, Kelestimur F (2014) Unusual effects of GH deficiency in adults: a review about the effects of GH on skin, sleep, and coagulation. Endocrine 47(3):679–689. doi:10.1007/s12020-014-0276-0

    Article  CAS  PubMed  Google Scholar 

  30. Tanriverdi F, Dokmetas HS, Kebapci N, Kilicli F, Atmaca H, Yarman S, Ertorer ME, Erturk E, Bayram F, Tugrul A, Culha C, Cakir M, Mert M, Aydin H, Taskale M, Ersoz N, Canturk Z, Anaforoglu I, Ozkaya M, Oruk G, Hekimsoy Z, Kelestimur F, Erbas T (2014) Etiology of hypopituitarism in tertiary care institutions in Turkish population: analysis of 773 patients from Pituitary Study Group database. Endocrine 47(1):198–205. doi:10.1007/s12020-013-0127-4

    Article  CAS  PubMed  Google Scholar 

  31. Popovic V (2013) Approach to testing growth hormone (GH) secretion in obese subjects. J Clin Endocrinol Metab 98(5):1789–1796. doi:10.1210/jc.2013-1099

    Article  CAS  PubMed  Google Scholar 

  32. Conceicao FL, da Costa e Silva A, Leal Costa AJ, Vaisman M (2003) Glucagon stimulation test for the diagnosis of GH deficiency in adults. J Endocrinol Invest 26(11):1065–1070

    Article  CAS  PubMed  Google Scholar 

  33. Brabant G, Poll EM, Jonsson P, Polydorou D, Kreitschmann-Andermahr I (2009) Etiology, baseline characteristics, and biochemical diagnosis of GH deficiency in the adult: are there regional variations? Eur J Endocrinol 161(Suppl 1):S25–S31. doi:10.1530/EJE-09-0273

    Article  CAS  PubMed  Google Scholar 

  34. Yuen KC, Biller BM, Katznelson L, Rhoads SA, Gurel MH, Chu O, Corazzini V, Spiller K, Gordon MB, Salvatori R, Cook DM (2013) Clinical characteristics, timing of peak responses and safety aspects of two dosing regimens of the glucagon stimulation test in evaluating growth hormone and cortisol secretion in adults. Pituitary 16(2):220–230. doi:10.1007/s11102-012-0407-7

    Article  CAS  PubMed  Google Scholar 

  35. Clemmons DR (2011) Consensus statement on the standardization and evaluation of growth hormone and insulin-like growth factor assays. Clin Chem 57(4):555–559. doi:10.1373/clinchem.2010.150631

    Article  CAS  PubMed  Google Scholar 

  36. Hartman ML, Crowe BJ, Biller BM, Ho KK, Clemmons DR, Chipman JJ (2002) Which patients do not require a GH stimulation test for the diagnosis of adult GH deficiency? J Clin Endocrinol Metab 87(2):477–485. doi:10.1210/jcem.87.2.8216

    Article  CAS  PubMed  Google Scholar 

  37. Aimaretti G, Corneli G, Baldelli R, Di Somma C, Gasco V, Durante C, Ausiello L, Rovere S, Grottoli S, Tamburrano G, Ghigo E (2003) Diagnostic reliability of a single IGF-I measurement in 237 adults with total anterior hypopituitarism and severe GH deficiency. Clin Endocrinol (Oxf) 59(1):56–61

    Article  CAS  Google Scholar 

  38. Russell-Aulet M, Dimaraki EV, Jaffe CA, DeMott-Friberg R, Barkan AL (2001) Aging-related growth hormone (GH) decrease is a selective hypothalamic GH-releasing hormone pulse amplitude mediated phenomenon. J Gerontol A Biol Sci Med Sci 56(2):M124–M129

    Article  CAS  PubMed  Google Scholar 

  39. Veldhuis JD, Iranmanesh A, Ho KK, Waters MJ, Johnson ML, Lizarralde G (1991) Dual defects in pulsatile growth hormone secretion and clearance subserve the hyposomatotropism of obesity in man. J Clin Endocrinol Metab 72(1):51–59. doi:10.1210/jcem-72-1-51

    Article  CAS  PubMed  Google Scholar 

  40. Kelestimur F, Popovic V, Leal A, Van Dam PS, Torres E, Perez Mendez LF, Greenman Y, Koppeschaar HP, Dieguez C, Casanueva FF (2006) Effect of obesity and morbid obesity on the growth hormone (GH) secretion elicited by the combined GHRH + GHRP-6 test. Clin Endocrinol (Oxf) 64(6):667–671

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Endocrinology, Erciyes University Medical School, 38039, Kayseri, Turkey

    Halit Diri, Zuleyha Karaca, Yasin Simsek, Fatih Tanriverdi, Kursad Unluhizarci & Fahrettin Kelestimur

  2. Department of Neurosurgery, Erciyes University Medical School, Kayseri, Turkey

    Ahmet Selcuklu

Authors
  1. Halit Diri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zuleyha Karaca
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yasin Simsek
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fatih Tanriverdi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kursad Unluhizarci
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ahmet Selcuklu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Fahrettin Kelestimur
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fahrettin Kelestimur.

Ethics declarations

Conflict of interest

None.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Diri, H., Karaca, Z., Simsek, Y. et al. Can a glucagon stimulation test characterized by lower GH cut-off value be used for the diagnosis of growth hormone deficiency in adults?. Pituitary 18, 884–892 (2015). https://doi.org/10.1007/s11102-015-0666-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11102-015-0666-1

Keywords

Search

Navigation