Abstract
Background
In patients with suspected acromegaly, evaluation of IGF-I is recommended as first-line test, while the assessment of GH-nadir during oral glucose tolerance test (OGTT) is advised as confirmatory test. The procedure of this test generally involves GH measurement every 30 min (30’) from baseline to +120’ or +180’. However, the optimal timing of samplings for the distinction between patients with or without active acromegaly is still a matter of debate.
Methods
Sixty-seven healthy subjects and 46 acromegalic patients who achieved documented and persistent long-term cure were enrolled. A greedy algorithm was used to identify the minimal subset of time-points that sufficed to correctly detect GH suppression.
Results
The sampling at 90’ was the one in which a GH level < 1 μg/L was most frequently achieved (i.e., in 91.3% of cured acromegalic patients and in 91.0% of healthy subjects). Considering the whole cohort, the best combination of 2 time-points was +90’ and +150’ and achieved 95.6% accuracy; the best combination of 3 time-points was +60’, +90’ and +150’ and achieved 99.1% accuracy. The minimal subset of GH determinations that demonstrated perfect accuracy (100%) needed the inclusion of 4 time-points, namely +60’, +90’, +120’ and +150’.
Conclusion
A subset of 4 time-points (60’ – 90’ – 120’ – 150’) was identified as the most relevant to detect GH suppression at OGTT, with a perfect classification of 100% of subjects. This supports the possibility to restrict the blood samplings to these time-points when assessing disease cure, with possible advantages in terms of saving time and lowering costs.
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Availability of data and material
The datasets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.
Code availability
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References
Katznelson L, Laws ER, Melmed S, Molitch ME, Murad MH, Utz A et al (2014) Acromegaly: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 99(11):3933–3951
Melmed S, Bronstein MD, Chanson P, Klibanski A, Casanueva FF, Wass JAH et al (2018) A consensus statement on acromegaly therapeutic outcomes. Nat Rev Endocrinol 14(9):552–561
Caputo M, Ucciero A, Mele C, De Marchi L, Magnani C, Cena T et al (2019) Use of administrative health databases to estimate incidence and prevalence of acromegaly in Piedmont Region, Italy. J Endocrinol Invest 42(4):397–402
Drange MR, Fram NR, Herman-Bonert V, Melmed S (2000) Pituitary tumor registry: a novel clinical resource 1. J Clin Endocrinol Metab 85(1):168–174
Molitch M (1992) Clinical manifestations of acromegaly. Endocrinol Metab Clin North Am 21(3):597–614
Pivonello R, Auriemma RS, Grasso LFS, Pivonello C, Simeoli C, Patalano R et al (2017) Complications of acromegaly: cardiovascular, respiratory and metabolic comorbidities. Pituitary 20(1):46–62
Rokkas T, Pistiolas D, Sechopoulos P, Margantinis G, Koukoulis G (2008) Risk of colorectal neoplasm in patients with acromegaly: a meta-analysis. World J Gastroenterol 14(22):3484–3489
Dekkers OM, Biermasz NR, Pereira AM, Romijn JA, Vandenbroucke JP (2008) Mortality in acromegaly: a metaanalysis. J Clin Endocrinol Metab 93(1):61–67
Colao A, Ferone D, Marzullo P, Lombardi G (2004) Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocr Rev 25(1):102–152
Kannan S, Kennedy L (2013) Diagnosis of acromegaly: State of the art. Expert Opin Med Diagn 7(5):443–453
Stoffel-Wagner B, Springer W, Bidlingmaier F, Klingmüller D (1997) A comparison of different methods for diagnosing acromegaly. Clin Endocrinol (Oxf) 46(5):531–537
Freda PU, Post KD, Powell JS, Wardlaw SL (1998) Evaluation of disease status with sensitive measures of growth hormone secretion in 60 postoperative patients with acromegaly 1. J Clin Endocrinol Metab 83(11):3808–3816
Freda PU, Reyes CM, Nuruzzaman AT, Sundeen RE, Bruce JN (2003) Basal and glucose-suppressed GH levels less than 1 μg/L in newly diagnosed acromegaly. Pituitary 6(4):175–180
Kim EH, Oh MC, Lee EJ, Kim SH (2012) Predicting long-term remission by measuring immediate postoperative growth hormone levels and oral glucose tolerance test in acromegaly. Neurosurgery 70(5):1106–1112
Vierhapper H, Heinze G, Gessl A, Exner M, Bieglmayr C (2003) Use of the oral glucose tolerance test to define remission in acromegaly. Metabolism 52(2):181–185
Giustina A, Chanson P, Bronstein MD, Klibanski A, Lamberts S, Casanueva FF et al (2010) A consensus on criteria for cure of acromegaly. J Clin Endocrinol Metabol Endocrine Soc. https://doi.org/10.1210/jc.2009-2670
Grottoli S, Razzore P, Gaia D, Gasperi M, Giusti M, Colao A 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. https://doi.org/10.1007/BF03345139
De Marinis L, Mancini A, Bianchi A, Gentilella R, Valle D, Giampietro A et al (2002) Preoperative growth hormone response to thyrotropin-releasing hormone and oral glucose tolerance test in acromegaly: A retrospective evaluation of 50 patients. Metabolism 51(5):616–621
Minuto F, Resmini E, Boschetti M, Arvigo M, Sormani MP, Giusti M et al (2004) Assessment of disease activity in acromegaly by means of a single blood sample: Comparison of the 120th minute postglucose value with spontaneous GH secretion and with the IGF system. Clin Endocrinol (Oxf) 61(1):138–144
Edmonds J (1971) Matroids and the greedy algorithm. Mathem Programm. 1(1):127–136
Bouchet A (1987) Greedy algorithm and symmetric matroids. Mathem Programm 38(2):147–159
Rajesh Khanna K, Shirisha M, Kauda BP (2021) A review of approaches and associated dimensions with greedy method for research implementations. Mater Today Proc. https://doi.org/10.1016/j.matpr.2021.01.691
Yamada S, Fukuhara N, Nishioka H, Takeshita A, Suzuki H, Miyakawa M et al (2011) GH deficiency in patients after cure of acromegaly by surgery alone. Eur J Endocrinol 165(6):873–879
Mazziotti G, Marzullo P, Doga M, Aimaretti G, Giustina A (2015) Growth hormone deficiency in treated acromegaly. Trends Endocrinol Metab 26(1):11–21
Ku CR, Hong JW, Kim EH, Kim SH, Lee EJ (2014) Clinical predictors of GH deficiency in surgically cured acromegalic patients. Eur J Endocrinol 171(3):379–387
Ronchi CL, Giavoli C, Ferrante E, Verrua E, Bergamaschi S, Ferrari DI et al (2009) Prevalence of GH deficiency in cured acromegalic patients: Impact of different previous treatments. Eur J Endocrinol 161(1):37–42
Giavoli C, Profka E, Verrua E, Ronchi CL, Ferrante E, Bergamaschi S et al (2012) GH replacement improves quality of life and metabolic parameters in cured acromegalic patients with growth hormone deficiency. J Clin Endocrinol Metab 97(11):3983–3988
Bidlingmaier M, Strasburger CJ (2007) Growth hormone assays: Current methodologies and their limitations. Pituitary 10(2):115–119
Bidlingmaier M (2008) Problems with GH assays and strategies toward standardization. Eur J Endocrinol. https://doi.org/10.1530/EJE-08-0284
Guha N (2013) Assays for GH, IGF-I, and IGF binding protein-3. Methods Mol Biol 1065:117–128
Schilbach K, Bidlingmaier M (2019) Laboratory investigations in the diagnosis and follow-up of GH-related disorders. Arch Endocrinol Metab 63(6):618–629
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
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Nunzia Prencipe and Silvia Grottoli are members of the Editorial Board of the Journal of Endocrinological Investigation; the other authors report no conflict of interest in this work.
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Bioletto, F., Prencipe, N., Berton, A.M. et al. Optimal timing of blood samplings to detect GH inhibition during oral glucose tolerance test. J Endocrinol Invest 45, 981–987 (2022). https://doi.org/10.1007/s40618-021-01731-0
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DOI: https://doi.org/10.1007/s40618-021-01731-0