ACTH and Cortisol Responses to Ghrelin and Desmopressin in Patients with Cushing's Disease and Adrenal Enlargement

Overview

Journal J Endocrinol Invest

Publisher Springer

Specialty Endocrinology

Date 2010 Feb 10

PMID 20142632

Citations 1

Authors

D Miljic

M Joksimovic

M Doknic

M Ivovic

M Djurovic

S Pekic

M Tancic

I Soldatovic

M Stojanovic

Dj Nale

Dj Macut

S Damjanovic

V Popovic

Affiliations

Soon will be listed here.

Abstract

Background: Overexpression of ghrelin and vasopressin (V3) receptors demonstrated on corticotrophe adenomas accounts for exaggerated ACTH and cortisol responses to ghrelin and desmopressin (DDAVP) in patients with Cushing's disease (CD).

Aim: In this study we have compared ACTH and cortisol responsiveness to DDAVP and ghrelin in CD patients with and without adrenal enlargement.

Subjects And Methods: Ghrelin and DDAVP tests were performed in 15 patients with CD (7 with and 8 without signs of adrenal enlargement) with CRH test in 8 patients. In 7 age and sex-matched healthy subjects, ghrelin test was performed. Plasma ACTH and serum cortisol concentrations were measured after ghrelin, DDAVP and CRH. Growth hormone was measured after stimulation with ghrelin.

Results: Significantly higher baseline and peak ACTH and cortisol concentrations after ghrelin were observed in all patients with CD compared to healthy control subjects. Patients with CD and adrenal enlargement had significantly lower baseline and peak ACTH concentrations after stimulation with ghrelin compared to CD patients without adrenal enlargement, while cortisol levels at baseline and after ghrelin administration were similar. Three out of seven patients with CD and adrenal enlargement did not respond to DDAVP while they responded well to CRH and ghrelin.

Conclusion: Patients with CD and adrenal enlargement pose special diagnostic problems. They may have lower baseline ACTH levels and may not respond to DDAVP while they respond to ghrelin and CRH. Despite increased endogenous cortisol levels in CD, cortisol responses to ghrelin and CRH are preserved in patients with CD and adrenal enlargement.

Citing Articles

Clinical review: The human experience with ghrelin administration.

Garin M, Burns C, Kaul S, Cappola A J Clin Endocrinol Metab. 2013; 98(5):1826-37.

PMID: 23533240 PMC: 3644599. DOI: 10.1210/jc.2012-4247.

References

Newell-Price J, Perry L, Medbak S, Monson J, Savage M, Besser M . A combined test using desmopressin and corticotropin-releasing hormone in the differential diagnosis of Cushing's syndrome. J Clin Endocrinol Metab. 1997; 82(1):176-81. DOI: 10.1210/jcem.82.1.3674. View

Gnanapavan S, Kola B, Bustin S, Morris D, McGee P, Fairclough P . The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J Clin Endocrinol Metab. 2002; 87(6):2988. DOI: 10.1210/jcem.87.6.8739. View

Barlier A, Zamora A, Grino M, Gunz G, Morange-Ramos I, Figarella-Branger D . Expression of functional growth hormone secretagogue receptors in human pituitary adenomas: polymerase chain reaction, triple in-situ hybridization and cell culture studies. J Neuroendocrinol. 1999; 11(7):491-502. DOI: 10.1046/j.1365-2826.1999.00351.x. View

Dahia P, Jacobs R, Chew S, Honegger J, Fahlbusch R, Besser G . Vasopressin receptor expression and mutation analysis in corticotropin-secreting tumors. J Clin Endocrinol Metab. 1996; 81(5):1768-71. DOI: 10.1210/jcem.81.5.8626831. View

de Keyzer Y, Lenne F, Auzan C, Jegou S, Rene P, Vaudry H . The pituitary V3 vasopressin receptor and the corticotroph phenotype in ectopic ACTH syndrome. J Clin Invest. 1996; 97(5):1311-8. PMC: 507185. DOI: 10.1172/JCI118547. View

Marova E, Goncharov N, Kolesnikova G, Arapova S, Lapshina A . The response of corticotropin and adrenal steroids to desmopressin stimulation in patients with various forms of hypercortisolism. Hormones (Athens). 2008; 7(3):243-50. DOI: 10.14310/horm.2002.1204. View

Skinner M, Nass R, Lopes B, Laws E, Thorner M . Growth hormone secretagogue receptor expression in human pituitary tumors. J Clin Endocrinol Metab. 1998; 83(12):4314-20. DOI: 10.1210/jcem.83.12.5307. View

Oliveira J, Vieira J, Abucham J, Lengyel A . GHRP-6 is able to stimulate cortisol and ACTH release in patients with Cushing's disease: comparison with DDAVP. J Endocrinol Invest. 2003; 26(3):230-5. DOI: 10.1007/BF03345162. View

de Keyzer Y, Rene P, Beldjord C, Lenne F, Bertagna X . Overexpression of vasopressin (V3) and corticotrophin-releasing hormone receptor genes in corticotroph tumours. Clin Endocrinol (Oxf). 1999; 49(4):475-82. DOI: 10.1046/j.1365-2265.1998.00560.x. View

10.

Leal-Cerro A, Torres E, Soto A, Dios E, Deghenghi R, Arvat E . Ghrelin is no longer able to stimulate growth hormone secretion in patients with Cushing's syndrome but instead induces exaggerated corticotropin and cortisol responses. Neuroendocrinology. 2003; 76(6):390-6. DOI: 10.1159/000067586. View

11.

Tsagarakis S, Vasiliou V, Kokkoris P, Stavropoulos G, Thalassinos N . Assessment of cortisol and ACTH responses to the desmopressin test in patients with Cushing's syndrome and simple obesity. Clin Endocrinol (Oxf). 1999; 51(4):473-7. DOI: 10.1046/j.1365-2265.1999.00830.x. View

12.

Imai T, Sarkar D, Shibata A, Funahashi H, Kikumori T, Ohmori S . Expression of adrenocorticotropin receptor gene in adrenocortical adenomas from patients with Cushing syndrome: possible contribution for the autonomous production of cortisol. Ann Surg. 2001; 234(1):85-91. PMC: 1421952. DOI: 10.1097/00000658-200107000-00013. View

13.

Tsagarakis S, Tsigos C, Vasiliou V, Tsiotra P, Kaskarelis J, Sotiropoulou C . The desmopressin and combined CRH-desmopressin tests in the differential diagnosis of ACTH-dependent Cushing's syndrome: constraints imposed by the expression of V2 vasopressin receptors in tumors with ectopic ACTH secretion. J Clin Endocrinol Metab. 2002; 87(4):1646-53. DOI: 10.1210/jcem.87.4.8358. View

14.

Kim K, Arai K, Sanno N, Osamura R, Teramoto A, Shibasaki T . Ghrelin and growth hormone (GH) secretagogue receptor (GHSR) mRNA expression in human pituitary adenomas. Clin Endocrinol (Oxf). 2001; 54(6):759-68. DOI: 10.1046/j.1365-2265.2001.01286.x. View

15.

Correa-Silva S, Nascif S, Lengyel A . Decreased GH secretion and enhanced ACTH and cortisol release after ghrelin administration in Cushing's disease: comparison with GH-releasing peptide-6 (GHRP-6) and GHRH. Pituitary. 2006; 9(2):101-7. DOI: 10.1007/s11102-006-9149-8. View

16.

Suda T, Kageyama K, Nigawara T, Sakihara S . Evaluation of diagnostic tests for ACTH-dependent Cushing's syndrome. Endocr J. 2009; 56(3):469-76. DOI: 10.1507/endocrj.k08e-353. View

17.

Arlt W, Dahia P, Callies F, Nordmeyer J, Allolio B, Grossman A . Ectopic ACTH production by a bronchial carcinoid tumour responsive to desmopressin in vivo and in vitro. Clin Endocrinol (Oxf). 1998; 47(5):623-7. DOI: 10.1046/j.1365-2265.1997.3091129.x. View

18.

Arnaldi G, Mancini T, Kola B, Appolloni G, Freddi S, Concettoni C . Cyclical Cushing's syndrome in a patient with a bronchial neuroendocrine tumor (typical carcinoid) expressing ghrelin and growth hormone secretagogue receptors. J Clin Endocrinol Metab. 2003; 88(12):5834-40. DOI: 10.1210/jc.2003-030514. View

19.

Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K . Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999; 402(6762):656-60. DOI: 10.1038/45230. View

20.

Korbonits M, Bustin S, Kojima M, Jordan S, Adams E, Lowe D . The expression of the growth hormone secretagogue receptor ligand ghrelin in normal and abnormal human pituitary and other neuroendocrine tumors. J Clin Endocrinol Metab. 2001; 86(2):881-7. DOI: 10.1210/jcem.86.2.7190. View