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Published in: Endocrine 3/2017

01-06-2017 | Original Article

Biochemical assessment of disease control in acromegaly: reappraisal of the glucose suppression test in somatostatin analogue (SA) treated patients

Authors: Mai Christiansen Arlien-Søborg, Christian Trolle, Elin Alvarson, Amanda Bæk, Jakob Dal, Jens Otto Lunde Jørgensen

Published in: Endocrine | Issue 3/2017

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Abstract

Background

It is recommended not to measure growth hormone during oral glucose suppression (oral glucose tolerance test) during somatostatin analog treatment in acromegaly. However, we have observed that failure to suppress growth hormone in response to oral glucose tolerance test during somatostatin analog unmasks insufficient disease control and hypothesize that somatostatin analog also induces insufficient growth hormone suppression to mixed meals.

Methods

We therefore compared serum growth hormone levels during two mixed meals in patients with controlled insulin-like growth factor-I levels after either surgery alone (n = 9) or somatostatin analog treatment (n = 9). The patients were unbiasedly matched for gender and insulin-like growth factor-I and studied twice in the following order: (1) during a 6 h growth hormone day curve including two mixed meals and (2) during a 3 h growth hormone profile including 60 min fasting followed by a 2-h oral glucose tolerance test.

Results

During the day curve growth hormone levels were elevated in the somatostatin analog group (P = 0.008) and growth hormone levels 1 h after each meal declined significantly only in the surgery group (P = 0.02). During the oral glucose tolerance test the two groups had similar growth hormone levels prior to the glucose load (P = 0.6), whereas a significant 66% suppression was observed after glucose only in the surgery group (P = 0.001).

Conclusions

(1) Patients controlled by somatostatin analog fail to suppress growth hormone in response to both mixed meals and oral glucose tolerance test (2) This phenomenon is likely to result in elevated serum growth hormone levels during everyday life in somatostatin analog-treated patients, (3) We postulate that measuring growth hormone levels during oral glucose tolerance test is useful to unmask potential somatostatin analog under-treatment in the presence of ‘safe’ insulin-like growth factor-I levels.
Literature
2.
go back to reference I.M. Holdaway, M.J. Bolland, G.D. Gamble, A meta-analysis of the effect of lowering serum levels of GH and IGF-I on mortality in acromegaly. Eur. J. Endocrinol. 159(2), 89–95 (2008). doi:10.1530/EJE-08-0267 CrossRefPubMed I.M. Holdaway, M.J. Bolland, G.D. Gamble, A meta-analysis of the effect of lowering serum levels of GH and IGF-I on mortality in acromegaly. Eur. J. Endocrinol. 159(2), 89–95 (2008). doi:10.​1530/​EJE-08-0267 CrossRefPubMed
3.
go back to reference 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). doi:10.1210/jc.2014-2700 CrossRefPubMed 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). doi:10.​1210/​jc.​2014-2700 CrossRefPubMed
4.
go back to reference B. Swearingen, F.G. Barker 2nd, L. Katznelson, B.M. Biller, S. Grinspoon, A. Klibanski, N. Moayeri, P.M. Black, N.T. Zervas, Long-term mortality after transsphenoidal surgery and adjunctive therapy for acromegaly. J. Clin. Endocrinol. Metab. 83(10), 3419–3426 (1998). doi:10.1210/jcem.83.10.5222 PubMed B. Swearingen, F.G. Barker 2nd, L. Katznelson, B.M. Biller, S. Grinspoon, A. Klibanski, N. Moayeri, P.M. Black, N.T. Zervas, Long-term mortality after transsphenoidal surgery and adjunctive therapy for acromegaly. J. Clin. Endocrinol. Metab. 83(10), 3419–3426 (1998). doi:10.​1210/​jcem.​83.​10.​5222 PubMed
5.
go back to reference A. Giustina, P. Chanson, M.D. Bronstein, A. Klibanski, S. Lamberts, F.F. Casanueva, P. Trainer, E. Ghigo, K. Ho, S. Melmed, G. Acromegaly Consensus, A consensus on criteria for cure of acromegaly. J. Clin. Endocrinol. Metab. 95(7), 3141–3148 (2010). doi:10.1210/jc.2009-2670 CrossRefPubMed A. Giustina, P. Chanson, M.D. Bronstein, A. Klibanski, S. Lamberts, F.F. Casanueva, P. Trainer, E. Ghigo, K. Ho, S. Melmed, G. Acromegaly Consensus, A consensus on criteria for cure of acromegaly. J. Clin. Endocrinol. Metab. 95(7), 3141–3148 (2010). doi:10.​1210/​jc.​2009-2670 CrossRefPubMed
6.
go back to reference J.D. Carmichael, V.S. Bonert, J.M. Mirocha, S. Melmed, 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 (2009). doi:10.1210/jc.2008-1371 CrossRefPubMed J.D. Carmichael, V.S. Bonert, J.M. Mirocha, S. Melmed, 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 (2009). doi:10.​1210/​jc.​2008-1371 CrossRefPubMed
7.
go back to reference G. Reimondo, M. Bondanelli, M.R. Ambrosio, F. Grimaldi, B. Zaggia, M.C. Zatelli, B. Allasino, F. Laino, E. Aroasio, A. Termine, P. Conton, A. Paoletta, E. Demenis, E.D. Uberti, M. Terzolo, Growth hormone values after an oral glucose load do not add clinically useful information in patients with acromegaly on long-term somatostatin receptor ligand treatment. Endocrine 45(1), 122–127 (2014). doi:10.1007/s12020-013-9996-9 CrossRefPubMed G. Reimondo, M. Bondanelli, M.R. Ambrosio, F. Grimaldi, B. Zaggia, M.C. Zatelli, B. Allasino, F. Laino, E. Aroasio, A. Termine, P. Conton, A. Paoletta, E. Demenis, E.D. Uberti, M. Terzolo, Growth hormone values after an oral glucose load do not add clinically useful information in patients with acromegaly on long-term somatostatin receptor ligand treatment. Endocrine 45(1), 122–127 (2014). doi:10.​1007/​s12020-013-9996-9 CrossRefPubMed
8.
go back to reference O. Alexopoulou, M. Bex, R. Abs, G. T’Sjoen, B. Velkeniers, D. Maiter, 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 (2008). doi:10.1210/jc.2007-2104 CrossRefPubMed O. Alexopoulou, M. Bex, R. Abs, G. T’Sjoen, B. Velkeniers, D. Maiter, 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 (2008). doi:10.​1210/​jc.​2007-2104 CrossRefPubMed
9.
go back to reference P.U. Freda, A.T. Nuruzzaman, C.M. Reyes, R.E. Sundeen, K.D. Post, 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 (2004). doi:10.1210/jc.2003-031316 CrossRefPubMed P.U. Freda, A.T. Nuruzzaman, C.M. Reyes, R.E. Sundeen, K.D. Post, 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 (2004). doi:10.​1210/​jc.​2003-031316 CrossRefPubMed
10.
go back to reference K.G. Alberti, N.J. Christensen, S.E. Christensen, A.P. Hansen, J. Iversen, K. Lundbaek, K. Seyer-Hansen, H. Orskov, Inhibition of insulin secretion by somatostatin. Lancet 2(7841), 1299–1301 (1973)CrossRefPubMed K.G. Alberti, N.J. Christensen, S.E. Christensen, A.P. Hansen, J. Iversen, K. Lundbaek, K. Seyer-Hansen, H. Orskov, Inhibition of insulin secretion by somatostatin. Lancet 2(7841), 1299–1301 (1973)CrossRefPubMed
11.
go back to reference M.I. Wurzburger, G.M. Prelevic, P.H. Sonksen, L.A. Balint-Peric, M. Wheeler, The effect of recombinant human growth hormone on regulation of growth hormone secretion and blood glucose in insulin-dependent diabetes. J. Clin. Endocrinol. Metab. 77(1), 267–272 (1993). doi:10.1210/jcem.77.1.8325951 PubMed M.I. Wurzburger, G.M. Prelevic, P.H. Sonksen, L.A. Balint-Peric, M. Wheeler, The effect of recombinant human growth hormone on regulation of growth hormone secretion and blood glucose in insulin-dependent diabetes. J. Clin. Endocrinol. Metab. 77(1), 267–272 (1993). doi:10.​1210/​jcem.​77.​1.​8325951 PubMed
12.
go back to reference K.Z. Rubeck, M. Madsen, C.M. Andreasen, S. Fisker, J. Frystyk, J.O. Jorgensen, Conventional and novel biomarkers of treatment outcome in patients with acromegaly: discordant results after somatostatin analog treatment compared with surgery. Eur. J. Endocrinol. 163(5), 717–726 (2010). doi:10.1530/EJE-10-0640 CrossRefPubMed K.Z. Rubeck, M. Madsen, C.M. Andreasen, S. Fisker, J. Frystyk, J.O. Jorgensen, Conventional and novel biomarkers of treatment outcome in patients with acromegaly: discordant results after somatostatin analog treatment compared with surgery. Eur. J. Endocrinol. 163(5), 717–726 (2010). doi:10.​1530/​EJE-10-0640 CrossRefPubMed
13.
go back to reference J. Frystyk, B. Dinesen, H. Orskov, Non-competitive time-resolved immunofluorometric assays for determination of human insulin-like growth factor I and II. Growth Regul. 5(4), 169–176 (1995)PubMed J. Frystyk, B. Dinesen, H. Orskov, Non-competitive time-resolved immunofluorometric assays for determination of human insulin-like growth factor I and II. Growth Regul. 5(4), 169–176 (1995)PubMed
14.
go back to reference N.R. Biermasz, A.M. Pereira, M. Frolich, J.A. Romijn, J.D. Veldhuis, F. Roelfsema, Octreotide represses secretory-burst mass and nonpulsatile secretion but does not restore event frequency or orderly GH secretion in acromegaly. Am. J. Physiol. Endocrinol. Metab. 286(1), E25–30 (2004). doi:10.1152/ajpendo.00230.2003 CrossRefPubMed N.R. Biermasz, A.M. Pereira, M. Frolich, J.A. Romijn, J.D. Veldhuis, F. Roelfsema, Octreotide represses secretory-burst mass and nonpulsatile secretion but does not restore event frequency or orderly GH secretion in acromegaly. Am. J. Physiol. Endocrinol. Metab. 286(1), E25–30 (2004). doi:10.​1152/​ajpendo.​00230.​2003 CrossRefPubMed
19.
go back to reference T. Krusenstjerna-Hafstrom, E.T. Vestergaard, M. Buhl, R. Nielsen, B.F. Clasen, S. Nielsen, N. Moller, S.B. Pedersen, J.O. Jorgensen, Acute peripheral metabolic effects of intraarterial leg infusion of somatostatin in healthy young men. J. Clin. Endocrinol. Metab. 96(8), 2581–2589 (2011). doi:10.1210/jc.2011-0592 CrossRefPubMed T. Krusenstjerna-Hafstrom, E.T. Vestergaard, M. Buhl, R. Nielsen, B.F. Clasen, S. Nielsen, N. Moller, S.B. Pedersen, J.O. Jorgensen, Acute peripheral metabolic effects of intraarterial leg infusion of somatostatin in healthy young men. J. Clin. Endocrinol. Metab. 96(8), 2581–2589 (2011). doi:10.​1210/​jc.​2011-0592 CrossRefPubMed
20.
go back to reference M.R. Gadelha, M.D. Bronstein, T. Brue, M. Coculescu, M. Fleseriu, M. Guitelman, V. Pronin, G. Raverot, I. Shimon, K.K. Lievre, J. Fleck, M. Aout, A.M. Pedroncelli, A. Colao, C.S.G. Pasireotide, Pasireotide versus continued treatment with octreotide or lanreotide in patients with inadequately controlled acromegaly (PAOLA): a randomised, phase 3 trial. Lancet Diabetes Endocrinol. 2(11), 875–884 (2014). doi:10.1016/S2213-8587(14)70169-X CrossRefPubMed M.R. Gadelha, M.D. Bronstein, T. Brue, M. Coculescu, M. Fleseriu, M. Guitelman, V. Pronin, G. Raverot, I. Shimon, K.K. Lievre, J. Fleck, M. Aout, A.M. Pedroncelli, A. Colao, C.S.G. Pasireotide, Pasireotide versus continued treatment with octreotide or lanreotide in patients with inadequately controlled acromegaly (PAOLA): a randomised, phase 3 trial. Lancet Diabetes Endocrinol. 2(11), 875–884 (2014). doi:10.​1016/​S2213-8587(14)70169-X CrossRefPubMed
21.
go back to reference G. Mazziotti, I. Floriani, S. Bonadonna, V. Torri, P. Chanson, A. Giustina, Effects of somatostatin analogs on glucose homeostasis: a metaanalysis of acromegaly studies. J. Clin. Endocrinol. Metab. 94(5), 1500–1508 (2009). doi:10.1210/jc.2008-2332 CrossRefPubMed G. Mazziotti, I. Floriani, S. Bonadonna, V. Torri, P. Chanson, A. Giustina, Effects of somatostatin analogs on glucose homeostasis: a metaanalysis of acromegaly studies. J. Clin. Endocrinol. Metab. 94(5), 1500–1508 (2009). doi:10.​1210/​jc.​2008-2332 CrossRefPubMed
Metadata
Title
Biochemical assessment of disease control in acromegaly: reappraisal of the glucose suppression test in somatostatin analogue (SA) treated patients
Authors
Mai Christiansen Arlien-Søborg
Christian Trolle
Elin Alvarson
Amanda Bæk
Jakob Dal
Jens Otto Lunde Jørgensen
Publication date
01-06-2017
Publisher
Springer US
Published in
Endocrine / Issue 3/2017
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-017-1258-9

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