Abstract
The biochemical assessment for newly recognized acromegaly is in most, but not all patients straightforward. Although significant improvements in the methods of biochemical testing for acromegaly have recently been made, major pitfalls to the assessment of this disease still exist. A number of different schemes have been employed for the assessment of GH secretion in clinical practice. Random GH levels have been often used, but remain unreliable for the assessment of acromegaly. Mean GH levels are also frequently used to assess GH status, but are not specific for the diagnosis of acromegaly. Measurement of glucose suppressed GH levels is the preferred method for assessing GH secretion in acromegaly. However, it is essential to recognize that when using highly sensitive and specific GH assays, nadir GH levels can be <1 μg/L after oral glucose in some patients with newly diagnosed acromegaly and postoperative patients with active disease. On the other hand, when using most clinically available commercial GH assays which are less sensitive and specific than those used in research studies, failure of GH suppression into the normal range set in these studies is not alone diagnostic of active acromegaly. In order to diagnose acromegaly, documentation of GH excess should be accompanied by elevation in levels of the GH dependent peptide, insulin-like growth factor I (IGF-I). Consideration also needs to be given to the clinical context in which GH and IGF-I are being measured as both can be altered in a number of clinical settings other than acromegaly. Both IGF-I and GH evaluations are important and complimentary parts of the biochemical assessment of acromegaly.
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References
Duncan E, Wass JA. Investigation protocol: Acromegaly and its investigation. Clin Endocrinol (Oxf) 1999;50:285–293.
Chang-DeMoranville BM, Jackson IM. Diagnosis and endocrine testing in acromegaly. Endocrinol Metab Clin North Am 1992;21:649–668.
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.
Hartman ML, Veldhuis JD, Thorner MO. Normal control of growth hormone secretion. Horm Res 1993;40:37–47.
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.
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: Aconsensus statement. J Clin Endocrinol Metab 2000;85:526–529.
Freda PU, Landman RE, Sundeen RE, Post KD. Gender and age in the biochemical assessment of cure of acromegaly. Pituitary 2001;4:163–171.
Ho KY, Weissberger AJ. Characterization of 24-hour growth hormone secretion in acromegaly: Implications for diagnosis and therapy. Clin Endocrinol (Oxf) 1994;41:75–83.
Hartman ML, Veldhuis JD, Vance ML, Faria AC, Furlanetto RW, Thorner MO. Somatotropin pulse frequency and basal concentrations are increased in acromegaly and are reduced by successful therapy. J Clin Endocrinol Metab 1990;70:1375–1384.
Peacey SR, Toogood AA, Veldhuis JD, Thorner MO, Shalet SM. 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 2001;86:259–266.
Peacey SR, Shalet SM. Insulin-like growth factor 1 measurement in diagnosis and management of acromegaly. Ann Clin Biochem 2001;38:297–303.
Bates AS, Evans AJ, Jones P, Clayton RN. Assessment of GH status in acromegaly using serum growth hormone, serum insulin-like growth factor-1 and urinary growth hormone excretion. Clin Endocrinol (Oxf) 1995;42:417–423.
Dobrashian RD, O'Halloran DJ, Hunt A, Beardwell CG, Shalet SM. Relationships between insulin-like growth factor-1 levels and growth hormone concentrations during diurnal profiles and following oral glucose in acromegaly. Clin Endocrinol (Oxf) 1993;38:589–593.
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.
Bates AS, Vanthoff W, Jones JM, Clayton RN. Does treatment of acromegaly affect life expectancy. Metabolism-Clinical and Experimental 1995;44:1–5.
Rajasoorya C, Holdaway IM, Wrightson P, Scott DJ, Ibbertson HK. Determinants of clinical outcome and survival in acromegaly. Clin Endocrinol (Oxf) 1994;41:95–102.
Freda PU. Current concepts in the biochemical assessment of the patient with acromegaly. Growth Hormone & IGF Research 2003;13:171–184.
Orme SM, McNally RJ, Cartwright RA, Belchetz PE. Mortality and cancer incidence in acromegaly: A retrospective cohort study. United Kingdom Acromegaly Study Group. J Clin Endocrinol Metab 1998;83:2730–2734.
Celniker AC, Chen AB, Wert RM, Jr, Sherman BM. Variability in the quantitation of circulating growth hormone using commercial immunoassays. J Clin Endocrinol Metab 1989;68:469–476.
Levin PA, Chalew SA, Martin L, Kowarski AA. Comparison of assays for growth hormone using monoclonal or polyclonal antibodies for diagnosis of growth disorders. J Lab Clin Med 1987;109:85–88.
Reiter EO, Morris AH, MacGillivray MH, Weber D. Variable estimates of serum growth hormone concentrations by different radioassay systems. J Clin Endocrinol Metab 1988;66:68–71.
Ebdrup L, Fisker S, Sorensen HH, Ranke MB, Orskov H. Variety in growth hormone determinations due to use of different immunoassays and to the interference of growth hormonebinding protein. Horm Res 1999;51(Suppl 1):20–26.
Seth J, Ellis A, Al-Sadie R. Serum growth hormone measurements in clinical practice: An audit of performance from the UK National External Quality Assessment scheme. Horm Res 1999;51(Suppl 1):13–19.
Hattori N, Shimatsu A, Kato Y, Koshiyama H, Ishikawa Y, Assadian H, Tanoh T, Nagao M, Imura H. 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 1990;70:771–776.
Stewart PM, Smith S, Seth J, Stewart SE, Cole D, Edwards CR. Normal growth hormone response to the 75 g oral glucose tolerance test measured by immunoradiometric assay. Ann Clin Biochem 1989;26(Pt 2):205–206.
De Marinis L, Mancini A, Bianchi A, Gentilella R, Valle D, Giampietro A, Zuppi P, Anile C, Maira G, Giustina A. Preoperative growth hormone response to thyrotropin-releasing hormone and oral glucose tolerance test in acromegaly: A retrospective evaluation of 50 patients. Metabolism 2002;51:616–621.
Costa AC, Rossi A, Martinelli CE Jr, 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.
Chapman IM, Hartman ML, Straume M, Johnson ML, Veldhuis JD, Thorner MO. Enhanced sensitivity growth hormone (GH) chemiluminescence assay reveals lower postglucose nadir GH concentrations in men than women. J Clin Endocrinol Metab 1994;78:1312–1319.
Bristow AF. International standards for growth hormone. Horm Res 1999;51(Suppl 1):7–12.
Ranke MB, Orskov H, Bristow AF, Seth J, Baumann G. Consensus on how to measure growth hormone in serum. Horm Res 1999;51(Suppl 1):27–29.
Pieters GF, Smals AG, Kloppenborg PW. Defective suppression of growth hormone after oral glucose loading in adolescence. J Clin Endocrinol Metab 1980;51:265–270.
Frantz AG, Rabkin MT. Effects of estrogen and sex difference on secretion of human growth hormone. J Clin Endocrinol Metab 1965;25:1470–1480.
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.
Pincus SM, Gevers EF, Robinson IC, van den Berg G, Roelfsema F, Hartman ML, Veldhuis JD. Females secrete growth hormone with more process irregularity than males in both humans and rats. Am J Physiol 1996;270:E107–E115.
Herlihy OM, Perros P. Elevated serum growth hormone in a patient with Type 1 diabetes: A diagnostic dilemma. Diabetes Metab Res Rev 2000;16:211–216.
Hall K, Hilding A, Thoren M. Determinants of circulating insulin-like growth factor-I. J Endocrinol Invest 1999;22:48–57.
LeRoith D, Clemmons D, Nissley P, Rechler MM. NIH conference. Insulin-like growth factors in health and disease [see comments]. Ann Intern Med 1992;116:854–862.
Merimee TJ, Zapf J, Froesch ER. Insulin-like growth factors in the fed and fasted states. J Clin Endocrinol Metab 1982;55:999–1002.
Clemmons DR, Van Wyk JJ. Factors controlling blood concentration of somatomedin C.Clin Endocrinol Metab 1984;13:113–143.
Smith WJ, Underwood LE, Clemmons DR. 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 1995;80:443–449.
Clemmons DR, Underwood LE. Nutritional regulation of IGF-I and IGF binding proteins. Annu Rev Nutr 1991;11:393–412.
Gama R, Labib M, Teale JD, Marks V. Acromegaly with a misleading normal plasma insulin-like growth factor 1. Ann Clin Biochem 1989;26(Pt 1):102–103.
Strasburger CJ, Bidlingmaier M, Wu Z, Morrison KM. Normal values of insulin-like growth factor I and their clinical utility in adults. Horm Res 2001;55(Suppl 2):100–105.
Hilding A, Hall K, Wivall-Helleryd IL, Saaf M, Melin AL, Thoren M. Serum levels of insulin-like growth factor I in 152 patients with growth hormone deficiency, aged 19–82 years, in relation to those in healthy subjects. J Clin Endocrinol Metab 1999;84:2013–2019.
Landin-Wilhelmsen K, Wilhelmsen L, Lappas G, Rosen T, Lindstedt G, Lundberg PA, Bengtsson BA. Serum insulin-like growth factor I in a random population sample of men and women: Relation to age, sex, smoking habits, coffee consumption and physical activity, blood pressure and concentrations of plasma lipids, fibrinogen, parathyroid hormone and osteocalcin. Clin Endocrinol (Oxf) 1994;41:351–357.
Ghigo E, Aimaretti G, Gianotti L, Bellone J, Arvat E, Camanni F. New approach to the diagnosis of growth hormone deficiency in adults. Eur J Endocrinol 1996;134:352–356.
Parkinson C, Ryder WD, Trainer PJ. The relationship between serum GH and serum IGF-I in acromegaly is gender-specific. J Clin Endocrinol Metab 2001;86:5240–5244.
Gomez JM, Maravall FJ, Gomez N, Navarro MA, Casamitjana R, Soler J. Interactions between serum leptin, the insulin-like growth factor-I system, and sex, age, anthropometric and body composition variables in a healthy population randomly selected. Clin Endocrinol (Oxf) 2003;58:213–219.
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.
Ho KY, Evans WS, Blizzard RM, Veldhuis JD, Merriam GR, Samojlik E, Furlanetto R, Rogol AD, Kaiser DL, Thorner MO. 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 1987;64: 51–58.
Cardim HJ, Lopes CM, Giannella-Neto D, da Fonseca AM, Pinotti JA. The insulin-like growth factor-I system and hormone replacement therapy. Fertil Steril 2001;75:282–287.
Weissberger AJ, Ho KK, Lazarus L. 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 1991;72:374–381.
Schalch DS, Kalayoglu M, Pirsch JD, Yang H, Raslich M, Rajpal S. Serum insulin-like growth factors and their binding proteins in patients with hepatic failure and after liver transplantation. Metabolism 1998;47:200–206.
Miell JP, Taylor AM, Zini M, Maheshwari HG, Ross RJ, Valcavi R. Effects of hypothyroidism and hyperthyroidism on insulin-like growth factors (IGFs) and growth hormone-and IGF-binding proteins. J Clin Endocrinol Metab 1993;76:950–955.
Feld S, Hirschberg R. Growth hormone, the insulin-like growth factor system, and the kidney. Endocr Rev 1996;17:423–480.
Goldberg AC, Trivedi B, Delmez JA, Harter HR, Daughaday WH. Uremia reduces serum insulin-like growth factor I, increases insulin-like growth factor II, and modifies their serum protein binding. J Clin Endocrinol Metab 1982;55:1040–1045.
Frystyk J, Ivarsen P, Skjaerbaek C, Flyvbjerg A, Pedersen EB, Orskov H. Serum-free insulin-like growth factor I correlates with clearance in patients with chronic renal failure. Kidney Int 1999;56:2076–2084.
Wong NA, Ahlquist JA, Camacho-Hubner C, Goodwin CJ, Dattani M, Marshall NJ, Wass JA. Acromegaly or chronic renal failure: A diagnostic dilemma. Clin Endocrinol (Oxf) 1997;46:221–226.
Clemmons DR. Commercial assays available for insulin-like growth factor I and their use in diagnosing growth hormone deficiency. Horm Res 2001;55(Suppl 2):73–79.
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Freda, P.U. Pitfalls in the Biochemical Assessment of Acromegaly. Pituitary 6, 135–140 (2003). https://doi.org/10.1023/B:PITU.0000011174.79946.10
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DOI: https://doi.org/10.1023/B:PITU.0000011174.79946.10