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Erschienen in: Pituitary 1/2015

01.02.2015

Salivary cortisol is a useful tool to assess the early response to pasireotide in patients with Cushing’s disease

verfasst von: Laura Trementino, Marina Cardinaletti, Carolina Concettoni, Giorgia Marcelli, Barbara Polenta, Maurizio Spinello, Marco Boscaro, Giorgio Arnaldi

Erschienen in: Pituitary | Ausgabe 1/2015

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Abstract

Purpose

Late night salivary cortisol (LNSC) is useful for diagnosing hypercortisolism and monitoring patients with Cushing’s disease (CD) following pituitary surgery. It may also be a better index of cortisol secretion than serum cortisol or urinary free cortisol (UFC). No data regarding the role of LNSC in the early monitoring of patients with CD receiving drug therapy has been published. We investigated the value of LNSC in monitoring the short-term efficacy of pasireotide.

Methods

Seven patients who were enrolled in a phase II study investigating the efficacy of pasireotide in CD (CSOM230B2208) were included in this analysis. Patients self-administered subcutaneous pasireotide 600 μg bid for 15 days. LNSC and UFC levels were assessed at baseline and day 15.

Results

At baseline, all patients had elevated LNSC which was correlated significantly with UFC levels (r = 0.97, P = .0002). At day 15, LNSC was reduced in six patients. LNSC decreases were observed from day 1 (−20 %) and persisted until day 15 (overall mean reduction from baseline −51 %), with the greatest decrease on day 5 (−58 %). At day 15, UFC levels were decreased in all patients and normalized in one that restored also salivary cortisol rhythm.

Conclusions

In patients with CD, pasireotide rapidly reduced and normalized both UFC and LNSC levels. LNSC may be a simple, non-invasive biomarker to assess the early response to pasireotide, particularly in determining whether cortisol rhythm is normalized in patients with normalized UFC levels. Further studies are warranted.
Literatur
1.
Zurück zum Zitat Arnaldi G, Angeli A, Atkinson AB, Bertagna X, Cavagnini F, Chrousos GP, Fava GA, Findling JW, Gaillard RC, Grossman AB, Kola B, Lacroix A, Mancini T, Mantero F, Newell-Price J, Nieman LK, Sonino N, Vance ML, Giustina A, Boscaro M (2003) Diagnosis and complications of Cushing’s syndrome: a consensus statement. J Clin Endocrinol Metab 88(12):5593–5602PubMedCrossRef Arnaldi G, Angeli A, Atkinson AB, Bertagna X, Cavagnini F, Chrousos GP, Fava GA, Findling JW, Gaillard RC, Grossman AB, Kola B, Lacroix A, Mancini T, Mantero F, Newell-Price J, Nieman LK, Sonino N, Vance ML, Giustina A, Boscaro M (2003) Diagnosis and complications of Cushing’s syndrome: a consensus statement. J Clin Endocrinol Metab 88(12):5593–5602PubMedCrossRef
2.
Zurück zum Zitat Arnaldi G, Mancini T, Tirabassi G, Trementino L, Boscaro M (2012) Advances in the epidemiology, pathogenesis, and management of Cushing’s syndrome complications. J Endocrinol Invest 35(4):434–448PubMedCrossRef Arnaldi G, Mancini T, Tirabassi G, Trementino L, Boscaro M (2012) Advances in the epidemiology, pathogenesis, and management of Cushing’s syndrome complications. J Endocrinol Invest 35(4):434–448PubMedCrossRef
3.
Zurück zum Zitat Biller BM, Grossman AB, Stewart PM, Melmed S, Bertagna X, Bertherat J, Buchfelder M, Colao A, Hermus AR, Hofland LJ, Klibanski A, Lacroix A, Lindsay JR, Newell-Price J, Nieman LK, Petersenn S, Sonino N, Stalla GK, Swearingen B, Vance ML, Wass JA, Boscaro M (2008) Treatment of adrenocorticotropin-dependent Cushing’s syndrome: a consensus statement. J Clin Endocrinol Metab 93(7):2454–2462PubMedCentralPubMedCrossRef Biller BM, Grossman AB, Stewart PM, Melmed S, Bertagna X, Bertherat J, Buchfelder M, Colao A, Hermus AR, Hofland LJ, Klibanski A, Lacroix A, Lindsay JR, Newell-Price J, Nieman LK, Petersenn S, Sonino N, Stalla GK, Swearingen B, Vance ML, Wass JA, Boscaro M (2008) Treatment of adrenocorticotropin-dependent Cushing’s syndrome: a consensus statement. J Clin Endocrinol Metab 93(7):2454–2462PubMedCentralPubMedCrossRef
4.
Zurück zum Zitat Hofland LJ, Lamberts SW (2003) The pathophysiological consequences of somatostatin receptor internalization and resistance. Endocr Rev 24(1):28–47PubMedCrossRef Hofland LJ, Lamberts SW (2003) The pathophysiological consequences of somatostatin receptor internalization and resistance. Endocr Rev 24(1):28–47PubMedCrossRef
5.
Zurück zum Zitat Batista DL, Zhang X, Gejman R, Ansell PJ, Zhou Y, Johnson SA, Swearingen B, Hedley-Whyte ET, Stratakis CA, Klibanski A (2006) The effects of SOM230 on cell proliferation and adrenocorticotropin secretion in human corticotroph pituitary adenomas. J Clin Endocrinol Metab 91(11):4482–4488PubMedCrossRef Batista DL, Zhang X, Gejman R, Ansell PJ, Zhou Y, Johnson SA, Swearingen B, Hedley-Whyte ET, Stratakis CA, Klibanski A (2006) The effects of SOM230 on cell proliferation and adrenocorticotropin secretion in human corticotroph pituitary adenomas. J Clin Endocrinol Metab 91(11):4482–4488PubMedCrossRef
6.
Zurück zum Zitat Bruns C, Lewis I, Briner U, Meno-Tetang G, Weckbecker G (2002) SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile. Eur J Endocrinol 146(5):707–716PubMedCrossRef Bruns C, Lewis I, Briner U, Meno-Tetang G, Weckbecker G (2002) SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile. Eur J Endocrinol 146(5):707–716PubMedCrossRef
7.
Zurück zum Zitat Hofland LJ, van der Hoek J, Feelders R, van Aken MO, van Koetsveld PM, Waaijers M, Sprij-Mooij D, Bruns C, Weckbecker G, de Herder WW, Beckers A, Lamberts SW (2005) The multi-ligand somatostatin analogue SOM230 inhibits ACTH secretion by cultured human corticotroph adenomas via somatostatin receptor type 5. Eur J Endocrinol 152(4):645–654PubMedCrossRef Hofland LJ, van der Hoek J, Feelders R, van Aken MO, van Koetsveld PM, Waaijers M, Sprij-Mooij D, Bruns C, Weckbecker G, de Herder WW, Beckers A, Lamberts SW (2005) The multi-ligand somatostatin analogue SOM230 inhibits ACTH secretion by cultured human corticotroph adenomas via somatostatin receptor type 5. Eur J Endocrinol 152(4):645–654PubMedCrossRef
8.
Zurück zum Zitat van der Hoek J, Waaijers M, van Koetsveld PM, Sprij-Mooij D, Feelders RA, Schmid HA, Schoeffter P, Hoyer D, Cervia D, Taylor JE, Culler MD, Lamberts SW, Hofland LJ (2005) Distinct functional properties of native somatostatin receptor subtype 5 compared with subtype 2 in the regulation of ACTH release by corticotroph tumor cells. Am J Physiol Endocrinol Metab 289(2):E278–E287PubMedCrossRef van der Hoek J, Waaijers M, van Koetsveld PM, Sprij-Mooij D, Feelders RA, Schmid HA, Schoeffter P, Hoyer D, Cervia D, Taylor JE, Culler MD, Lamberts SW, Hofland LJ (2005) Distinct functional properties of native somatostatin receptor subtype 5 compared with subtype 2 in the regulation of ACTH release by corticotroph tumor cells. Am J Physiol Endocrinol Metab 289(2):E278–E287PubMedCrossRef
9.
Zurück zum Zitat Boscaro M, Ludlam WH, Atkinson B, Glusman JE, Petersenn S, Reincke M, Snyder P, Tabarin A, Biller BM, Findling J, Melmed S, Darby CH, Hu K, Wang Y, Freda PU, Grossman AB, Frohman LA, Bertherat J (2009) Treatment of pituitary-dependent Cushing’s disease with the multireceptor ligand somatostatin analog pasireotide (SOM230): a multicenter, phase II trial. J Clin Endocrinol Metab 94(1):115–122PubMedCrossRef Boscaro M, Ludlam WH, Atkinson B, Glusman JE, Petersenn S, Reincke M, Snyder P, Tabarin A, Biller BM, Findling J, Melmed S, Darby CH, Hu K, Wang Y, Freda PU, Grossman AB, Frohman LA, Bertherat J (2009) Treatment of pituitary-dependent Cushing’s disease with the multireceptor ligand somatostatin analog pasireotide (SOM230): a multicenter, phase II trial. J Clin Endocrinol Metab 94(1):115–122PubMedCrossRef
10.
Zurück zum Zitat Colao A, Petersenn S, Newell-Price J, Findling JW, Gu F, Maldonado M, Schoenherr U, Mills D, Salgado LR, Biller BM (2012) Pasireotide B2305 study group: a 12-month phase 3 study of pasireotide in Cushing’s disease. N Engl J Med 366(10):914–924PubMedCrossRef Colao A, Petersenn S, Newell-Price J, Findling JW, Gu F, Maldonado M, Schoenherr U, Mills D, Salgado LR, Biller BM (2012) Pasireotide B2305 study group: a 12-month phase 3 study of pasireotide in Cushing’s disease. N Engl J Med 366(10):914–924PubMedCrossRef
11.
Zurück zum Zitat Nieman LK, Biller BM, Findling JW, Newell-Price J, Savage MO, Stewart PM, Montori VM (2008) The diagnosis of Cushing’s syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 93(5):1526–1540PubMedCentralPubMedCrossRef Nieman LK, Biller BM, Findling JW, Newell-Price J, Savage MO, Stewart PM, Montori VM (2008) The diagnosis of Cushing’s syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 93(5):1526–1540PubMedCentralPubMedCrossRef
12.
Zurück zum Zitat Papanicolaou DA, Mullen N, Kyrou I, Nieman LK (2002) Nighttime salivary cortisol: a useful test for the diagnosis of Cushing’s syndrome. J Clin Endocrinol Metab 87(10):4515–4521PubMedCrossRef Papanicolaou DA, Mullen N, Kyrou I, Nieman LK (2002) Nighttime salivary cortisol: a useful test for the diagnosis of Cushing’s syndrome. J Clin Endocrinol Metab 87(10):4515–4521PubMedCrossRef
13.
Zurück zum Zitat Putignano P, Toja P, Dubini A, Pecori Giraldi F, Corsello SM, Cavagnini F (2003) Midnight salivary cortisol versus urinary free and midnight serum cortisol as screening tests for Cushing’s syndrome. J Clin Endocrinol Metab 88(9):4153–4157PubMedCrossRef Putignano P, Toja P, Dubini A, Pecori Giraldi F, Corsello SM, Cavagnini F (2003) Midnight salivary cortisol versus urinary free and midnight serum cortisol as screening tests for Cushing’s syndrome. J Clin Endocrinol Metab 88(9):4153–4157PubMedCrossRef
14.
Zurück zum Zitat Raff H, Raff JL, Findling JW (1998) Late-night salivary cortisol as a screening test for Cushing’s syndrome. J Clin Endocrinol Metab 83(8):2681–2686PubMed Raff H, Raff JL, Findling JW (1998) Late-night salivary cortisol as a screening test for Cushing’s syndrome. J Clin Endocrinol Metab 83(8):2681–2686PubMed
15.
Zurück zum Zitat Viardot A, Huber P, Puder JJ, Zulewski H, Keller U, Müller B (2005) Reproducibility of nighttime salivary cortisol and its use in the diagnosis of hypercortisolism compared with urinary free cortisol and overnight dexamethasone suppression test. J Clin Endocrinol Metab 90(10):5730–5736PubMedCrossRef Viardot A, Huber P, Puder JJ, Zulewski H, Keller U, Müller B (2005) Reproducibility of nighttime salivary cortisol and its use in the diagnosis of hypercortisolism compared with urinary free cortisol and overnight dexamethasone suppression test. J Clin Endocrinol Metab 90(10):5730–5736PubMedCrossRef
16.
Zurück zum Zitat Yaneva M, Mosnier-Pudar H, Dugué MA, Grabar S, Fulla Y, Bertagna X (2004) Midnight salivary cortisol for the initial diagnosis of Cushing’s syndrome of various causes. J Clin Endocrinol Metab 89(7):3345–3351PubMedCrossRef Yaneva M, Mosnier-Pudar H, Dugué MA, Grabar S, Fulla Y, Bertagna X (2004) Midnight salivary cortisol for the initial diagnosis of Cushing’s syndrome of various causes. J Clin Endocrinol Metab 89(7):3345–3351PubMedCrossRef
17.
Zurück zum Zitat Raff H (2012) Cushing’s syndrome: diagnosis and surveillance using salivary cortisol. Pituitary 15(1):64–70PubMedCrossRef Raff H (2012) Cushing’s syndrome: diagnosis and surveillance using salivary cortisol. Pituitary 15(1):64–70PubMedCrossRef
18.
Zurück zum Zitat Carrasco CA, Coste J, Guignat L, Groussin L, Dugué MA, Gaillard S, Bertagna X, Bertherat J (2008) Midnight salivary cortisol determination for assessing the outcome of transsphenoidal surgery in Cushing’s disease. J Clin Endocrinol Metab 93(12):4728–4734PubMedCrossRef Carrasco CA, Coste J, Guignat L, Groussin L, Dugué MA, Gaillard S, Bertagna X, Bertherat J (2008) Midnight salivary cortisol determination for assessing the outcome of transsphenoidal surgery in Cushing’s disease. J Clin Endocrinol Metab 93(12):4728–4734PubMedCrossRef
19.
Zurück zum Zitat Nunes ML, Vattaut S, Corcuff JB, Rault A, Loiseau H, Gatta B, Valli N, Letenneur L, Tabarin A (2009) Late-night salivary cortisol for diagnosis of overt and subclinical Cushing’s syndrome in hospitalized and ambulatory patients. J Clin Endocrinol Metab 94(2):456–462PubMedCrossRef Nunes ML, Vattaut S, Corcuff JB, Rault A, Loiseau H, Gatta B, Valli N, Letenneur L, Tabarin A (2009) Late-night salivary cortisol for diagnosis of overt and subclinical Cushing’s syndrome in hospitalized and ambulatory patients. J Clin Endocrinol Metab 94(2):456–462PubMedCrossRef
20.
Zurück zum Zitat Jonsson BA, Malmberg B, Amilon A, Helene Garde Am, Orbaek P (2003) Determination of cortisol in human saliva using liquid chromatography-electrospray tandem mass spectrometry. J Chromatogr B Anal Technol Biomed Life Sci 784(1):63–68CrossRef Jonsson BA, Malmberg B, Amilon A, Helene Garde Am, Orbaek P (2003) Determination of cortisol in human saliva using liquid chromatography-electrospray tandem mass spectrometry. J Chromatogr B Anal Technol Biomed Life Sci 784(1):63–68CrossRef
21.
Zurück zum Zitat Findling JW, Raff H (2006) Cushing’s syndrome: important issues in diagnosis and management. J Clin Endocrinol Metab 91(10):3746–3753PubMedCrossRef Findling JW, Raff H (2006) Cushing’s syndrome: important issues in diagnosis and management. J Clin Endocrinol Metab 91(10):3746–3753PubMedCrossRef
22.
Zurück zum Zitat Ceccato F, Albiger N, Reimondo G, Frigo AC, Ferasin S, Occhi G, Mantero F, Terzolo M, Scaroni C (2012) Assessment of glucocorticoid therapy with salivary cortisol in secondary adrenal insufficiency. Eur J Endocrinol 167(6):769–776PubMedCrossRef Ceccato F, Albiger N, Reimondo G, Frigo AC, Ferasin S, Occhi G, Mantero F, Terzolo M, Scaroni C (2012) Assessment of glucocorticoid therapy with salivary cortisol in secondary adrenal insufficiency. Eur J Endocrinol 167(6):769–776PubMedCrossRef
23.
Zurück zum Zitat Newell-Price J, Petersenn S, Pivonello R, Findling J, Fleseriu M, Trovato A, Hughes G, Ligueros-Saylan M, Biller B (2013) Evaluation of late-night salivary cortisol during a phase III study with pasireotide in patients with Cushing’s disease [abstract]. Endocrine Abstracts 32:P853. doi:10.1530/endoabs.32.P853 Newell-Price J, Petersenn S, Pivonello R, Findling J, Fleseriu M, Trovato A, Hughes G, Ligueros-Saylan M, Biller B (2013) Evaluation of late-night salivary cortisol during a phase III study with pasireotide in patients with Cushing’s disease [abstract]. Endocrine Abstracts 32:P853. doi:10.​1530/​endoabs.​32.​P853
24.
Zurück zum Zitat Raff H (2009) Utility of salivary cortisol measurements in Cushing’s syndrome and adrenal insufficiency. J Clin Endocrinol Metab 94(10):3647–3655PubMedCrossRef Raff H (2009) Utility of salivary cortisol measurements in Cushing’s syndrome and adrenal insufficiency. J Clin Endocrinol Metab 94(10):3647–3655PubMedCrossRef
25.
Zurück zum Zitat Raff H, Findling JW (2003) A physiologic approach to diagnosis of the Cushing syndrome. Ann Intern Med 138:980–991PubMedCrossRef Raff H, Findling JW (2003) A physiologic approach to diagnosis of the Cushing syndrome. Ann Intern Med 138:980–991PubMedCrossRef
26.
Zurück zum Zitat Hellhammer DH, Wüst S, Kudielka BM (2009) Salivary cortisol as a biomarker in stress research. Psychoneuroendocrinology 34:163–171PubMedCrossRef Hellhammer DH, Wüst S, Kudielka BM (2009) Salivary cortisol as a biomarker in stress research. Psychoneuroendocrinology 34:163–171PubMedCrossRef
27.
Zurück zum Zitat Kidambi S, Raff H, Findling JW (2007) Limitations of nocturnal salivary cortisol and urine free cortisol in the diagnosis of mild Cushing’s syndrome. Eur J Endocrinol 157(6):725–731PubMedCrossRef Kidambi S, Raff H, Findling JW (2007) Limitations of nocturnal salivary cortisol and urine free cortisol in the diagnosis of mild Cushing’s syndrome. Eur J Endocrinol 157(6):725–731PubMedCrossRef
28.
Zurück zum Zitat Terzolo M, Bovio S, Pia A, Conton PA, Reimondo G, Dall’Asta C, Bemporad D, Angeli A, Opocher G, Mannelli M, Ambrosi B, Mantero F (2005) Midnight serum cortisol as a marker of increased cardiovascular risk in patients with a clinically inapparent adrenal adenoma. Eur J Endocrinol 153(2):307–315PubMedCrossRef Terzolo M, Bovio S, Pia A, Conton PA, Reimondo G, Dall’Asta C, Bemporad D, Angeli A, Opocher G, Mannelli M, Ambrosi B, Mantero F (2005) Midnight serum cortisol as a marker of increased cardiovascular risk in patients with a clinically inapparent adrenal adenoma. Eur J Endocrinol 153(2):307–315PubMedCrossRef
29.
Zurück zum Zitat Oltmanns KM, Dodt B, Schultes B, Raspe HH, Schweiger U, Born J, Fehm HL, Peters A (2006) Cortisol correlates with metabolic disturbances in a population study of type 2 diabetic patients. Eur J Endocrinol 154(2):325–331PubMedCrossRef Oltmanns KM, Dodt B, Schultes B, Raspe HH, Schweiger U, Born J, Fehm HL, Peters A (2006) Cortisol correlates with metabolic disturbances in a population study of type 2 diabetic patients. Eur J Endocrinol 154(2):325–331PubMedCrossRef
Metadaten
Titel
Salivary cortisol is a useful tool to assess the early response to pasireotide in patients with Cushing’s disease
verfasst von
Laura Trementino
Marina Cardinaletti
Carolina Concettoni
Giorgia Marcelli
Barbara Polenta
Maurizio Spinello
Marco Boscaro
Giorgio Arnaldi
Publikationsdatum
01.02.2015
Verlag
Springer US
Erschienen in
Pituitary / Ausgabe 1/2015
Print ISSN: 1386-341X
Elektronische ISSN: 1573-7403
DOI
https://doi.org/10.1007/s11102-014-0557-x

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