Skip to main content
Log in

Biochemical investigations in diagnosis and follow up of acromegaly

  • Published:
Pituitary Aims and scope Submit manuscript

Abstract

Measurements of human growth hormone (GH) and insulin-like growth-factor I (IGF-I) are cornerstones in the diagnosis of acromegaly. Both hormones are also used as biochemical markers in the evaluation of disease activity during treatment. Management of acromegaly is particularly challenging in cases where discordant information is obtained from measurement of GH concentrations following oral glucose load and from measurement of IGF-I. While in some patients biological factors can explain the discrepancy, in many cases issues with the analytical methods seem to be responsible. Assays used by endocrine laboratories to determine concentrations of GH and IGF-I underwent significant changes during the last decades. While generally leading to more sensitive and reproducible methods, these changes also had considerable impact on absolute concentrations measured. This must be reflected by updated decision limits, cut-offs and reference intervals. Since different commercially available assays do not agree very well, method specific interpretation of GH and IGF-I concentrations is required. This complexity in the interpretation of hormone concentrations is not always appropriately reflected in laboratory reports, but also not in clinical guidelines reporting decision limits not related to a specific analytical method. The present review provides an overview about methodological and biological variables affecting the biochemical assessment of acromegaly in diagnosis and follow up.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Rosario PW (2011) Frequency of acromegaly in adults with diabetes or glucose intolerance and estimated prevalence in the general population. Pituitary 14(3):217–221

    Article  CAS  PubMed  Google Scholar 

  2. Nabarro JD (1987) Acromegaly. Clin Endocrinol 26(4):481–512

    Article  CAS  Google Scholar 

  3. Rajasoorya C et al (1994) Determinants of clinical outcome and survival in acromegaly. Clin Endocrinol 41(1):95–102

    Article  CAS  Google Scholar 

  4. Nachtigall L et al (2008) Changing patterns in diagnosis and therapy of acromegaly over two decades. J Clin Endocrinol Metab 93(6):2035–2041

    Article  CAS  PubMed  Google Scholar 

  5. Reid TJ et al (2010) Features at diagnosis of 324 patients with acromegaly did not change from 1981 to 2006: acromegaly remains under-recognized and under-diagnosed. Clin Endocrinol 72(2):203–208

    Article  Google Scholar 

  6. Bates AS et al (1993) An audit of outcome of treatment in acromegaly. Q J Med 86(5):293–299

    CAS  PubMed  Google Scholar 

  7. Swearingen B et al (1998) Long-term mortality after transsphenoidal surgery and adjunctive therapy for acromegaly. J Clin Endocrinol Metab 83(10):3419–3426

    CAS  PubMed  Google Scholar 

  8. Colao A et al (2004) Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocr Rev 25(1):102–152

    Article  CAS  PubMed  Google Scholar 

  9. Holdaway IM, Rajasoorya RC, Gamble GD (2004) Factors influencing mortality in acromegaly. J Clin Endocrinol Metab 89(2):667–674

    Article  CAS  PubMed  Google Scholar 

  10. Szczesniak D, Jawiarczyk-Przybylowska A, Rymaszewska J (2015) The quality of life and psychological, social and cognitive functioning of patients with acromegaly. Adv Clin Exp Med 24(1):167–172

    Article  PubMed  Google Scholar 

  11. Ben-Shlomo A et al (2011) Clinical, quality of life, and economic value of acromegaly disease control. Pituitary 14(3):284–294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Laws ER Jr., et al (1979) Neurosurgical management of acromegaly. Results in 82 patients treated between 1972 and 1977. J Neurosurg 50(4):454–461

    Article  PubMed  Google Scholar 

  13. Colao A et al (2006) Age changes the diagnostic accuracy of mean profile and nadir growth hormone levels after oral glucose in postoperative patients with acromegaly. Clin Endocrinol 65(2):250–256

    Article  CAS  Google Scholar 

  14. Buchfelder M, Schlaffer SM (2016) The surgical treatment of acromegaly. Pituitary. doi:10.1007/s11102-016-0765-7

    Google Scholar 

  15. Katznelson L et al (2014) Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 99(11):3933–3951

    Article  CAS  PubMed  Google Scholar 

  16. Giustina A et al (2011) Current management practices for acromegaly: an international survey. Pituitary 14(2):125–133

    Article  CAS  PubMed  Google Scholar 

  17. Apaydin T et al (2016) Daily life reflections of acromegaly guidelines. J Endocrinol Invest. doi:10.1007/s40618-016-0567-9

    PubMed  Google Scholar 

  18. Melmed S (2009) Acromegaly pathogenesis and treatment. J Clin Invest 119(11):3189–3202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Salmon WD Jr, Daughaday WH (1957) A hormonally controlled serum factor which stimulates sulfate incorporation by cartilage in vitro. J Lab Clin Med 49(6):825–836

    CAS  PubMed  Google Scholar 

  20. Butz LB et al (2016) “Micromegaly”: an update on the prevalence of acromegaly with apparently normal GH secretion in the modern era. Pituitary. doi:10.1007/s11102-016-0735-0

    Google Scholar 

  21. Ribeiro-Oliveira A Jr, Faje AT, Barkan AL (2011) Limited utility of oral glucose tolerance test in biochemically active acromegaly. Eur J Endocrinol 164(1):17–22

    Article  CAS  PubMed  Google Scholar 

  22. Freda PU et al (2003) Basal and glucose-suppressed GH levels less than 1 microg/L in newly diagnosed acromegaly. Pituitary 6(4):175–180

    Article  CAS  PubMed  Google Scholar 

  23. Alexopoulou O et al (2008) Divergence between growth hormone and insulin-like growth factor-i concentrations in the follow-up of acromegaly. J Clin Endocrinol Metab 93(4):1324–1330

    Article  CAS  PubMed  Google Scholar 

  24. Elias PC et al (2010) Discordant nadir GH after oral glucose and IGF-I levels on treated acromegaly: refining the biochemical markers of mild disease activity. Horm Metab Res 42(1):50–55

    Article  CAS  PubMed  Google Scholar 

  25. Sherlock M et al (2009) Monitoring disease activity using GH and IGF-I in the follow-up of 501 patients with acromegaly. Clin Endocrinol 71(1):74–81

    Article  CAS  Google Scholar 

  26. Bianchi A et al (2009) Influence of growth hormone receptor d3 and full-length isoforms on biochemical treatment outcomes in acromegaly. J Clin Endocrinol Metab 94(6):2015–2022

    Article  CAS  PubMed  Google Scholar 

  27. Carmichael JD et al (2009) The utility of oral glucose tolerance testing for diagnosis and assessment of treatment outcomes in 166 patients with acromegaly. J Clin Endocrinol Metab 94(2):523–527

    Article  CAS  PubMed  Google Scholar 

  28. Freda PU et al (2001) Gender and age in the biochemical assessment of cure of acromegaly. Pituitary 4(3):163–171

    Article  CAS  PubMed  Google Scholar 

  29. Dimaraki EV et al (2002) Acromegaly with apparently normal GH secretion: implications for diagnosis and follow-up. J Clin Endocrinol Metab 87(8):3537–3542

    Article  CAS  PubMed  Google Scholar 

  30. Gullu S et al (2004) Remission criteria for the follow-up of patients with acromegaly. Eur J Endocrinol 150(4):465–471

    Article  CAS  PubMed  Google Scholar 

  31. Donaghy AJ et al (2002) Regulation of the growth hormone receptor/binding protein, insulin-like growth factor ternary complex system in human cirrhosis. J Hepatol 36(6):751–758

    Article  CAS  PubMed  Google Scholar 

  32. Verrua E et al (2011) GH response to oral glucose tolerance test: a comparison between patients with acromegaly and other pituitary disorders. J Clin Endocrinol Metab 96(1):E83–E88

    Article  CAS  PubMed  Google Scholar 

  33. Manolopoulou J et al (2012) Automated 22-kD growth hormone-specific assay without interference from pegvisomant. Clin Chem 58(10):1446–1456

    Article  CAS  PubMed  Google Scholar 

  34. Minuto FM et al (2012) Biochemical diagnosis and assessment of disease activity in acromegaly: a two-decade experience. Pituitary 15(2):215–221

    Article  PubMed  CAS  Google Scholar 

  35. Bancos I et al (2013) Determination of nadir growth hormone concentration cutoff in patients with acromegaly. Endocr Pract 19(6):937–945

    Article  PubMed  Google Scholar 

  36. Rosario PW, Calsolari MR (2015) Safety and specificity of the growth hormone suppression test in patients with diabetes. Endocr 48(1):329–333

    Article  CAS  Google Scholar 

  37. Frystyk J, Freda P, Clemmons DR (2010) The current status of IGF-I assays—a 2009 update. Growth Horm IGF Res 20(1):8–18

    Article  CAS  PubMed  Google Scholar 

  38. Bidlingmaier M, Freda PU (2010) Measurement of human growth hormone by immunoassays: current status, unsolved problems and clinical consequences. Growth Horm IGF Res 20(1):19–25

    Article  CAS  PubMed  Google Scholar 

  39. Ross DA, Wilson CB (1988) Results of transsphenoidal microsurgery for growth hormone-secreting pituitary adenoma in a series of 214 patients. J Neurosurg 68(6):854–867

    Article  CAS  PubMed  Google Scholar 

  40. Lindholm J et al (1987) Investigation of the criteria for assessing the outcome of treatment in acromegaly. Clin Endocrinol 27(5):553–562

    Article  CAS  Google Scholar 

  41. Abosch A et al (1998) Transsphenoidal microsurgery for growth hormone-secreting pituitary adenomas: initial outcome and long-term results. J Clin Endocrinol Metab 83(10):3411–3418

    Article  CAS  PubMed  Google Scholar 

  42. Melmed S et al (1995) Clinical review 75: recent advances in pathogenesis, diagnosis, and management of acromegaly. J Clin Endocrinol Metab 80(12):3395–3402

    CAS  PubMed  Google Scholar 

  43. Giustina A et al (2000) Criteria for cure of acromegaly: a consensus statement. J Clin Endocrinol Metab 85(2):526–529

    CAS  PubMed  Google Scholar 

  44. Giustina A et al (2010) A consensus on criteria for cure of acromegaly. J Clin Endocrinol Metab 95(7):3141–3148

    Article  CAS  PubMed  Google Scholar 

  45. Endert E et al (2006) Establishment of reference values for endocrine tests–part V: acromegaly. Neth J Med 64(7):230–235

    CAS  PubMed  Google Scholar 

  46. Freda PU et al (2004) 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 89(2):495–500

    Article  CAS  PubMed  Google Scholar 

  47. Freda PU et al (1998) Evaluation of disease status with sensitive measures of growth hormone secretion in 60 postoperative patients with acromegaly. J Clin Endocrinol Metab 83(11):3808–3816

    CAS  PubMed  Google Scholar 

  48. Chapman IM et al (1994) Enhanced sensitivity growth hormone (GH) chemiluminescence assay reveals lower postglucose nadir GH concentrations in men than women. J Clin Endocrinol Metab 78(6):1312–1319

    CAS  PubMed  Google Scholar 

  49. Baumann GP (2009) Growth hormone isoforms. Growth Horm IGF Res 19(4):333–340

    Article  CAS  PubMed  Google Scholar 

  50. Wieringa GE, Barth JH, Trainer PJ (2004) Growth hormone assay standardization: a biased view? Clin Endocrinol 60(5):538–539

    Article  CAS  Google Scholar 

  51. Sheppard MC (2007) Growth hormone assay standardization: an important clinical advance. Clin Endocrinol 66(2):157–161

    Article  CAS  Google Scholar 

  52. 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

    Article  CAS  PubMed  Google Scholar 

  53. Markkanen H et al (2006) Effect of sex and assay method on serum concentrations of growth hormone in patients with acromegaly and in healthy controls. Clin Chem 52(3):468–473

    Article  CAS  PubMed  Google Scholar 

  54. Granada ML et al (1990) Assay-dependent results of immunoassayable spontaneous 24-hour growth hormone secretion in short children. Acta Paediatr Scand Suppl 370:63–70 (discussion 71)

    Article  CAS  PubMed  Google Scholar 

  55. Celniker AC et al (1989) Variability in the quantitation of circulating growth hormone using commercial immunoassays. J Clin Endocrinol Metab 68(2):469–476

    Article  CAS  PubMed  Google Scholar 

  56. Arafat AM et al (2008) 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

    Article  CAS  PubMed  Google Scholar 

  57. Pokrajac A et al (2007) Variation in GH and IGF-I assays limits the applicability of international consensus criteria to local practice. Clin Endocrinol 67(1):65–70

    Article  CAS  Google Scholar 

  58. Hattori N et al (1990) 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

    Article  CAS  PubMed  Google Scholar 

  59. Costa AC et al (2002) 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 87(7):3142–3147

    Article  CAS  PubMed  Google Scholar 

  60. Grottoli S et al (2003) Three-hour spontaneous GH secretion profile is as reliable as oral glucose tolerance test for the diagnosis of acromegaly. J Endocrinol Invest 26(2):123–127

    Article  CAS  PubMed  Google Scholar 

  61. Rosario PW, Furtado MS (2008) Growth hormone after oral glucose overload: revision of reference values in normal subjects. Arq Bras Endocrinol Metabol 52(7):1139–1144

    Article  PubMed  Google Scholar 

  62. Arafat AM et al (2011) Comparison of oral glucose tolerance test (OGTT) 100 g with OGTT 75 g for evaluation of acromegalic patients and the impact of gender on test reproducibility. Clin Endocrinol 75(5):685–691

    Article  CAS  Google Scholar 

  63. Clemmons DR (2007) IGF-I assays: current assay methodologies and their limitations. Pituitary 10(2):121–128

    Article  CAS  PubMed  Google Scholar 

  64. Quarmby V, Quan C (1999) How much insulin-like growth factor-I (IGF-I) circulates?: impact of standardization on IGF-I assay accuracy. Dev Biol Stand 97:111–118

    CAS  PubMed  Google Scholar 

  65. Burns C et al (2009) The First International Standard For Insulin-like Growth Factor-1 (IGF-1) for immunoassay: preparation and calibration in an international collaborative study. Growth Horm IGF Res 19(5):457–462

    Article  CAS  PubMed  Google Scholar 

  66. Boero L et al (2012) Comparison of two immunoassays in the determination of IGF-I levels and its correlation with oral glucose tolerance test (OGTT) and with clinical symptoms in acromegalic patients. Pituitary 15(4):466–471

    Article  CAS  PubMed  Google Scholar 

  67. Bidlingmaier M et al (2014) Reference intervals for insulin-like growth factor-1 (igf-i) from birth to senescence: results from a multicenter study using a new automated chemiluminescence IGF-I immunoassay conforming to recent international recommendations. J Clin Endocrinol Metab 99(5):1712–1721

    Article  CAS  PubMed  Google Scholar 

  68. Chanson P et al (2016) Reference values for IGF-I serum concentrations: comparison of six immunoassays. J Clin Endocrinol Metab 101(9):3450–3458

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Rosario PW (2010) Measurement of basal GH in the diagnosis of acromegaly. Arq Bras Endocrinol Metabol 54(7):668–669

    Article  PubMed  Google Scholar 

  70. Jenkins D et al (1995) The Birmingham pituitary database: auditing the outcome of the treatment of acromegaly. Clin Endocrinol 43(5):517–522

    Article  CAS  Google Scholar 

  71. Freda PU (2003) Pitfalls in the biochemical assessment of acromegaly. Pituitary 6(3):135–140

    Article  CAS  PubMed  Google Scholar 

  72. Roelfsema F, Veldhuis JD (2016) Growth hormone dynamics in healthy adults are related to age and sex and strongly dependent on body mass index. Neuroendocrinology 103(3–4):335–344

    CAS  PubMed  Google Scholar 

  73. Peacey SR et al (2001) 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 86(1):259–266

    Article  CAS  PubMed  Google Scholar 

  74. Bates AS et al (1995) Assessment of GH status in acromegaly using serum growth hormone, serum insulin-like growth factor-1 and urinary growth hormone excretion. Clin Endocrinol 42(4):417–423

    Article  CAS  Google Scholar 

  75. Dobrashian RD et al (1993) Relationships between insulin-like growth factor-1 levels and growth hormone concentrations during diurnal profiles and following oral glucose in acromegaly. Clin Endocrinol 38(6):589–593

    Article  CAS  Google Scholar 

  76. Kaltsas GA et al (2001) 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 86(4):1645–1652

    Article  CAS  PubMed  Google Scholar 

  77. Jorgensen JO et al (1990) Pulsatile versus continuous intravenous administration of growth hormone (GH) in GH-deficient patients: effects on circulating insulin-like growth factor-I and metabolic indices. J Clin Endocrinol Metab 70(6):1616–1623

    Article  CAS  PubMed  Google Scholar 

  78. Laursen T et al (1995) Continuous infusion versus daily injections of growth hormone (GH) for 4 weeks in GH-deficient patients. J Clin Endocrinol Metab 80(8):2410–2418

    PubMed  Google Scholar 

  79. Johansson JO et al (1996) Two weeks of daily injections and continuous infusion of recombinant human growth hormone (GH) in GH-deficient adults: I. Effects on insulin-like growth factor-I (IGF-I), GH and IGF binding proteins, and glucose homeostasis. Metabolism 45(3):362–369

    Article  CAS  PubMed  Google Scholar 

  80. Feelders RA et al (2005) Postoperative evaluation of patients with acromegaly: clinical significance and timing of oral glucose tolerance testing and measurement of (free) insulin-like growth factor I, acid-labile subunit, and growth hormone-binding protein levels. J Clin Endocrinol Metab 90(12):6480–6489

    Article  CAS  PubMed  Google Scholar 

  81. Kreutzer J et al (2001) Surgical management of GH-secreting pituitary adenomas: an outcome study using modern remission criteria. J Clin Endocrinol Metab 86(9):4072–4077

    Article  CAS  PubMed  Google Scholar 

  82. Takahashi JA et al (2004) Early postoperative indicators of late outcome in acromegalic patients. Clin Endocrinol 60(3):366–374

    Article  Google Scholar 

  83. Espinosa-de-los-Monteros AL et al (2002) Changing patterns of insulin-like growth factor-I and glucose-suppressed growth hormone levels after pituitary surgery in patients with acromegaly. J Neurosurg 97(2):287–292

    Article  CAS  PubMed  Google Scholar 

  84. Hartman ML, Veldhuis JD, Thorner MO (1993) Normal control of growth hormone secretion. Horm Res 40(1–3):37–47

    Article  CAS  PubMed  Google Scholar 

  85. Jaffe CA et al (1998) Regulatory mechanisms of growth hormone secretion are sexually dimorphic. J Clin Invest 102(1):153–164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Hoeflich A, Russo VC (2015) Physiology and pathophysiology of IGFBP-1 and IGFBP-2—consensus and dissent on metabolic control and malignant potential. Best Pract Res Clin Endocrinol Metab 29(5):685–700

    Article  CAS  PubMed  Google Scholar 

  87. Clemmons DR (2016) Role of IGF binding proteins in regulating metabolism. Trends Endocrinol Metab 27(6):375–391

    Article  CAS  PubMed  Google Scholar 

  88. Growth Hormone Research S, S Pituitary (2004) Biochemical assessment and long-term monitoring in patients with acromegaly: statement from a joint consensus conference of the Growth Hormone Research Society and the Pituitary Society. J Clin Endocrinol Metab 89(7):3099–3102

    Article  CAS  Google Scholar 

  89. Frantz AG, Rabkin MT (1965) Effects of estrogen and sex difference on secretion of human growth hormone. J Clin Endocrinol Metab 25(11):1470–1480

    Article  CAS  PubMed  Google Scholar 

  90. Ho KY et al (1987) Effects of sex and age on the 24-hour profile of growth hormone secretion in man: importance of endogenous estradiol concentrations. J Clin Endocrinol Metab 64(1):51–58

    Article  CAS  PubMed  Google Scholar 

  91. Faria AC et al (1992) Pulsatile growth hormone release in normal women during the menstrual cycle. Clin Endocrinol 36(6):591–596

    Article  CAS  Google Scholar 

  92. Ronchi CL et al (2007) Adequacy of current postglucose GH nadir limit (<1 μg/L) to define long-lasting remission of acromegalic disease. Clin Endocrinol 66(4):538–542

    Article  CAS  Google Scholar 

  93. Dawson-Hughes B et al (1986) Regulation of growth hormone and somatomedin-C secretion in postmenopausal women: effect of physiological estrogen replacement. J Clin Endocrinol Metab 63(2):424–432

    Article  CAS  PubMed  Google Scholar 

  94. Weissberger AJ, Ho KK, Lazarus L (1991) Contrasting effects of oral and transdermal routes of estrogen replacement therapy on 24-hour growth hormone (GH) secretion, insulin-like growth factor I, and GH-binding protein in postmenopausal women. J Clin Endocrinol Metab 72(2):374–381

    Article  CAS  PubMed  Google Scholar 

  95. Engstrom BE, Karlsson FA, Wide L (1998) Marked gender differences in ambulatory morning growth hormone values in young adults. Clin Chem 44(6 Pt 1):1289–1295

    CAS  PubMed  Google Scholar 

  96. Colao A et al (2002) Gender- and age-related differences in the endocrine parameters of acromegaly. J Endocrinol Invest 25(6):532–538

    Article  CAS  PubMed  Google Scholar 

  97. Leung KC et al (2004) Estrogen regulation of growth hormone action. Endocr Rev 25(5):693–721

    Article  CAS  PubMed  Google Scholar 

  98. Strasburger CJ et al (2001) Normal values of insulin-like growth factor I and their clinical utility in adults. Horm Res 55(Suppl 2)100–105

    CAS  PubMed  Google Scholar 

  99. Clemmons DR, JJ Van Wyk (1984) Factors controlling blood concentration of somatomedin C. Clin Endocrinol Metab 13(1):113–143

    Article  CAS  PubMed  Google Scholar 

  100. Parkinson C et al (2002) Gender and age influence the relationship between serum GH and IGF-I in patients with acromegaly. Clin Endocrinol 57(1):59–64

    Article  CAS  Google Scholar 

  101. Parkinson C et al (2001) The relationship between serum GH and serum IGF-I in acromegaly is gender-specific. J Clin Endocrinol Metab 86(11):5240–5244

    Article  CAS  PubMed  Google Scholar 

  102. Wiedemann E, Schwartz E (1972) Suppression of growth hormone-dependent human serum sulfation factor by estrogen. J Clin Endocrinol 34:51–58

    Article  PubMed  Google Scholar 

  103. Clemmons DR et al (1980) Estradiol treatment of acromegaly. Reduction of immunoreactive somatomedin-C and improvement in metabolic status. Am J Med 69(4):571–575

    Article  CAS  PubMed  Google Scholar 

  104. Hobbs CJ et al (1993) Testosterone administration increases insulin-like growth factor-I levels in normal men. J Clin Endocrinol Metab 77(3):776–779

    CAS  PubMed  Google Scholar 

  105. Ghigo E et al (1996) New approach to the diagnosis of growth hormone deficiency in adults. Eur J Endocrinol 134(3):352–356

    Article  CAS  PubMed  Google Scholar 

  106. Vierhapper H et al (2003) Use of the oral glucose tolerance test to define remission in acromegaly. Metabolism 52(2):181–185

    Article  CAS  PubMed  Google Scholar 

  107. Juul A (2003) Serum levels of insulin-like growth factor I and its binding proteins in health and disease. Growth Horm IGF Res 13(4):113–170

    Article  CAS  PubMed  Google Scholar 

  108. Brick DJ et al (2010) Determinants of IGF1 and GH across the weight spectrum: from anorexia nervosa to obesity. Eur J Endocrinol 163(2):185–191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Galli G et al (2012) Serum insulin-like growth factor-1 concentrations are reduced in severely obese women and raise after weight loss induced by laparoscopic adjustable gastric banding. Obes Surg 22(8):1276–1280

    Article  PubMed  Google Scholar 

  110. Merimee TJ, Zapf J, Froesch ER (1982) Insulin-like growth factors in the fed and fasted states. J Clin Endocrinol Metab 55(5):999–1002

    Article  CAS  PubMed  Google Scholar 

  111. Smith WJ, Underwood LE, Clemmons DR (1995) Effects of caloric or protein restriction on insulin-like growth factor-I (IGF-I) and IGF-binding proteins in children and adults. J Clin Endocrinol Metab 80(2):443–449

    CAS  PubMed  Google Scholar 

  112. Clemmons DR, Underwood LE (1991) Nutritional regulation of IGF-I and IGF binding proteins. Annu Rev Nutr 11:393–412

    Article  CAS  PubMed  Google Scholar 

  113. Grottoli S et al (2008) Growth hormone/insulin-like growth factor I axis, glucose metabolism, and lypolisis but not leptin show some degree of refractoriness to short-term fasting in acromegaly. J Endocrinol Invest 31(12):1103–1109

    Article  CAS  PubMed  Google Scholar 

  114. Bartz S et al (2014) Severe acute malnutrition in childhood: hormonal and metabolic status at presentation, response to treatment, and predictors of mortality. J Clin Endocrinol Metab 99(6):2128–2137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Grinspoon SK et al (1995) Effects of rhIGF-I administration on bone turnover during short-term fasting. J Clin Invest 96(2):900–906

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Straus DS, Takemoto CD (1990) Effect of fasting on insulin-like growth factor-I (IGF-I) and growth hormone receptor mRNA levels and IGF-I gene transcription in rat liver. Mol Endocrinol 4(1):91–100

    Article  CAS  PubMed  Google Scholar 

  117. Stoving RK et al (1999) Jointly amplified basal and pulsatile growth hormone (GH) secretion and increased process irregularity in women with anorexia nervosa: indirect evidence for disruption of feedback regulation within the GH-insulin-like growth factor I axis. J Clin Endocrinol Metab 84(6):2056–2063

    CAS  PubMed  Google Scholar 

  118. Haffner D et al (1994) Metabolic clearance of recombinant human growth hormone in health and chronic renal failure. J Clin Invest 93(3):1163–1171

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Tonshoff B et al (1995) Deconvolution analysis of spontaneous nocturnal growth hormone secretion in prepubertal children with preterminal chronic renal failure and with end-stage renal disease. Pediatr Res 37(1):86–93

    Article  CAS  PubMed  Google Scholar 

  120. Tonshoff B et al (1997) Decreased hepatic insulin-like growth factor (IGF)-I and increased IGF binding protein-1 and -2 gene expression in experimental uremia. Endocrinology 138(3):938–946

    Article  CAS  PubMed  Google Scholar 

  121. Rabkin R (2001) Growth factor insensitivity in renal failure. Ren Fail 23(3–4):291–300

    Article  CAS  PubMed  Google Scholar 

  122. Hirschberg R, Adler S (1998) Insulin-like growth factor system and the kidney: physiology, pathophysiology, and therapeutic implications. Am J Kidney Dis 31(6):901–919

    Article  CAS  PubMed  Google Scholar 

  123. Powell DR et al (1999) Effects of chronic renal failure and growth hormone on serum levels of insulin-like growth factor-binding protein-4 (IGFBP-4) and IGFBP-5 in children: a report of the Southwest Pediatric Nephrology Study Group. J Clin Endocrinol Metab 84(2):596–601

    CAS  PubMed  Google Scholar 

  124. Anderwald CH et al (2014) Whole-body insulin sensitivity rather than body-mass-index determines fasting and post-glucose-load growth hormone concentrations. PLoS One 9(12):e115184

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  125. Giustina A et al (1990) Impaired growth hormone (GH) response to pyridostigmine in type 1 diabetic patients with exaggerated GH-releasing hormone-stimulated GH secretion. J Clin Endocrinol Metab 71(6):1486–1490

    Article  CAS  PubMed  Google Scholar 

  126. Giustina A et al (1991) Effects of exogenous growth hormone pretreatment on the pituitary growth hormone response to growth hormone-releasing hormone alone or in combination with pyridostigmine in type I diabetic patients. Acta Endocrinol 125(5):510–517

    CAS  PubMed  Google Scholar 

  127. Giustina A et al (1996) Hypothalamic control of growth hormone (GH) secretion in type I diabetic men: effect of the combined administration of GH-releasing hormone and hexarelin, a novel GHRP-6 analog. Endocr Res 22(2):159–174

    Article  CAS  PubMed  Google Scholar 

  128. Giustina A, Wehrenberg WB (1994) Growth Hormone neuroregulation in diabetes mellitus. Trends Endocrinol Metab 5(2):73–78

    Article  CAS  PubMed  Google Scholar 

  129. Giustina A et al (1994) Effect of pyridostigmine on the growth hormone response to growth hormone-releasing hormone in lean and obese type II diabetic patients. Metabolism 43(7):893–898

    Article  CAS  PubMed  Google Scholar 

  130. Giustina A et al (1992) Effect of galanin on the growth hormone response to growth hormone-releasing hormone in acromegaly. Metabolism 41(12):1291–1294

    Article  CAS  PubMed  Google Scholar 

  131. Mazziotti G et al (2008) Biochemical evaluation of patients with active acromegaly and type 2 diabetes mellitus: efficacy and safety of the galanin test. Neuroendocrinology 88(4):299–304

    Article  CAS  PubMed  Google Scholar 

  132. Giustina A et al (2015) Insulin and GH-IGF-I axis: endocrine pacer or endocrine disruptor? Acta Diabetol 52(3):433–443

    Article  CAS  PubMed  Google Scholar 

  133. Rinderknecht E, Humbel RE (1978) The amino acid sequence of human insulin-like growth factor I and its structural homology with proinsulin. J Biol Chem 253(8):2769–2776

    CAS  PubMed  Google Scholar 

  134. Boni-Schnetzler M et al (1991) Insulin regulates insulin-like growth factor I mRNA in rat hepatocytes. Am J Physiol 260(6 Pt 1):E846–E851

    CAS  PubMed  Google Scholar 

  135. Janssen JA, Lamberts SW (1999) Is the measurement of free IGF-I more indicative than that of total IGF-I in the evaluation of the biological activity of the GH/IGF-I axis? J Endocrinol Invest 22(4):313–315

    Article  CAS  PubMed  Google Scholar 

  136. Bereket A, Lang CH, Wilson TA (1999) Alterations in the growth hormone-insulin-like growth factor axis in insulin dependent diabetes mellitus. Horm Metab Res 31(2–3):172–181

    Article  CAS  PubMed  Google Scholar 

  137. Van den Berghe GH (1998) Acute and prolonged critical illness are two distinct neuroendocrine paradigms. Verh K Acad Geneeskd Belg 60(6):487–518 (discussion 518–20)

    PubMed  Google Scholar 

  138. Voerman HJ et al (1992) Growth hormone: secretion and administration in catabolic adult patients, with emphasis on the critically ill patient. Neth J Med 41(5–6):229–244

    CAS  PubMed  Google Scholar 

  139. Baxter RC et al (1998) Thirty-day monitoring of insulin-like growth factors and their binding proteins in intensive care unit patients. Growth Horm IGF Res 8(6):455–463

    Article  CAS  PubMed  Google Scholar 

  140. Ross R et al (1991) Critically ill patients have high basal growth hormone levels with attenuated oscillatory activity associated with low levels of insulin-like growth factor-I. Clin Endocrinol 35(1):47–54

    Article  CAS  Google Scholar 

  141. Elijah IE et al (2011) The GH/IGF-1 system in critical illness. Best Pract Res Clin Endocrinol Metab 25(5):759–767

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Van den Berghe G et al (1998) Neuroendocrinology of prolonged critical illness: effects of exogenous thyrotropin-releasing hormone and its combination with growth hormone secretagogues. J Clin Endocrinol Metab 83(2):309–319

    PubMed  Google Scholar 

  143. Van den Berghe G et al (1997) The somatotropic axis in critical illness: effect of continuous growth hormone (GH)-releasing hormone and GH-releasing peptide-2 infusion. J Clin Endocrinol Metab 82(2):590–599

    PubMed  Google Scholar 

  144. DeBoer MD et al (2016) Systemic inflammation, growth factors, and linear growth in the setting of infection and malnutrition. Nutrition. doi:10.1016/j.nut.2016.06.013

    PubMed  Google Scholar 

  145. Donaghy A et al (1995) Growth hormone, insulinlike growth factor-1, and insulinlike growth factor binding proteins 1 and 3 in chronic liver disease. Hepatology 21(3):680–688

    CAS  PubMed  Google Scholar 

  146. Cuneo RC et al (1995) Altered endogenous growth hormone secretory kinetics and diurnal GH-binding protein profiles in adults with chronic liver disease. Clin Endocrinol 43(3):265–275

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Martin Bidlingmaier.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Schilbach, K., Strasburger, C.J. & Bidlingmaier, M. Biochemical investigations in diagnosis and follow up of acromegaly. Pituitary 20, 33–45 (2017). https://doi.org/10.1007/s11102-017-0792-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11102-017-0792-z

Keywords

Navigation