Food-Dependent Cushing’s Syndrome: Possible Involvement of Leptin in Cortisol Hypersecretion1
François P. Pralong2,
Fulgencio Gomez,
Louis Guillou,
François Mosimann,
Sebastiano Franscella and
Rolf C. Gaillard
Division of Endocrinology, Diabetology, and Metabolism, Department
of Medicine, Institute of Pathology (F.M.), and the Department of
Surgery (L.G.), University Hospital and Lausanne Medical School, 1011
Lausanne, Switzerland
Address all correspondence and requests for reprints to: François P. Pralong, M.D., Division of Endocrinology, BH 19707, Centre Hospitalier Universitaive Vaudois, 1011 Lausanne, Switzerland. E-mail: francois.pralong{at}chuv.hospvd.ch
Stimulation of cortisol secretion by food intake has been implicatedin
the pathogenesis of some cases of ACTH-independent Cushing’ssyndrome,
via an aberrant response of the adrenal glands togastric inhibitory
polypeptide (GIP). We report here a novelcase of food-dependent
Cushing’s syndrome in a patientwith bilateral macronodular adrenal
hyperplasia. In this patientwe were able to confirm a paradoxical
stimulation of cortisolsecretion by GIP in vivo as well
as in vitro on dispersed tumoradrenal cells obtained at
surgery. In addition to GIP, in vitrostimulation of
these cultured tumor adrenal cells with leptin,the secreted product of
the adipocyte, induced cortisol secretion.By comparison, no such
stimulation was observed in vitro inadrenal cells
obtained from another patient with bilateral macronodularadrenal
hyperplasia and Cushing’s syndrome that did notdepend on food intake,
in tumor cells obtained from a solitarycortisol-secreting adrenal
adenoma, and in normal human adrenocorticalcells.
These results demonstrate that as in previously described casesof
food-dependent Cushing’s syndrome, GIP stimulated cortisolsecretion
from the adrenals of the patient reported here. Therefore,they
indicate that such a paradoxical response probably representsthe
hallmark of this rare condition. In addition, they suggestthat leptin,
which normally inhibits stimulated cortisol secretionin humans,
participated in cortisol hypersecretion in this case.Further studies
in other cases of food-dependent Cushing’ssyndrome, however, will be
necessary to better ascertain thepathophysiological significance of
this finding.
This article has been cited by other articles:
H.-P. Hsiao, L. S. Kirschner, I. Bourdeau, M. F. Keil, S. A. Boikos, S. Verma, A. J. Robinson-White, M. Nesterova, A. Lacroix, and C. A. Stratakis Clinical and Genetic Heterogeneity, Overlap with Other Tumor Syndromes, and Atypical Glucocorticoid Hormone Secretion in Adrenocorticotropin-Independent Macronodular Adrenal Hyperplasia Compared with Other Adrenocortical Tumors
J. Clin. Endocrinol. Metab.,
August 1, 2009;
94(8):
2930 - 2937.
[Abstract][Full Text][PDF]
N M Albiger, G Occhi, B Mariniello, M Iacobone, G Favia, A Fassina, D Faggian, F Mantero, and C Scaroni Food-dependent Cushing's syndrome: from molecular characterization to therapeutical results
Eur. J. Endocrinol.,
December 1, 2007;
157(6):
771 - 778.
[Abstract][Full Text][PDF]
A. Lampron, I. Bourdeau, P. Hamet, J. Tremblay, and A. Lacroix Whole Genome Expression Profiling of Glucose-Dependent Insulinotropic Peptide (GIP)- and Adrenocorticotropin-Dependent Adrenal Hyperplasias Reveals Novel Targets for the Study of GIP-Dependent Cushing's Syndrome
J. Clin. Endocrinol. Metab.,
September 1, 2006;
91(9):
3611 - 3618.
[Abstract][Full Text][PDF]
T. L. Mazzuco, O. Chabre, N. Sturm, J.-J. Feige, and M. Thomas Ectopic Expression of the Gastric Inhibitory Polypeptide Receptor Gene Is a Sufficient Genetic Event to Induce Benign Adrenocortical Tumor in a Xenotransplantation Model
Endocrinology,
February 1, 2006;
147(2):
782 - 790.
[Abstract][Full Text][PDF]
V. Baldacchino, S. Oble, P.-O. Decarie, I. Bourdeau, P. Hamet, J. Tremblay, and A. Lacroix The Sp transcription factors are involved in the cellular expression of the human glucose-dependent insulinotropic polypeptide receptor gene and overexpressed in adrenals of patients with Cushing's syndrome
J. Mol. Endocrinol.,
August 1, 2005;
35(1):
61 - 71.
[Abstract][Full Text][PDF]
L. Groussin, K. Perlemoine, V. Contesse, H. Lefebvre, A. Tabarin, P. Thieblot, J. L. Schlienger, J. P. Luton, X. Bertagna, and J. Bertherat The Ectopic Expression of the Gastric Inhibitory Polypeptide Receptor Is Frequent in Adrenocorticotropin-Independent Bilateral Macronodular Adrenal Hyperplasia, but Rare in Unilateral Tumors
J. Clin. Endocrinol. Metab.,
May 1, 2002;
87(5):
1980 - 1985.
[Abstract][Full Text][PDF]
I. Bourdeau, P. D'Amour, P. Hamet, J.-M. Boutin, and A. Lacroix Aberrant Membrane Hormone Receptors in Incidentally Discovered Bilateral Macronodular Adrenal Hyperplasia with Subclinical Cushing's Syndrome
J. Clin. Endocrinol. Metab.,
November 1, 2001;
86(11):
5534 - 5540.
[Abstract][Full Text][PDF]
N. Cherradi, A. M. Capponi, R. C. Gaillard, and F. P. Pralong Decreased Expression of Steroidogenic Acute Regulatory Protein: A Novel Mechanism Participating in the Leptin-Induced Inhibition of Glucocorticoid Biosynthesis
Endocrinology,
August 1, 2001;
142(8):
3302 - 3308.
[Abstract][Full Text][PDF]
A. Lacroix, N. N'Diaye, J. Tremblay, and P. Hamet Ectopic and Abnormal Hormone Receptors in Adrenal Cushing's Syndrome
Endocr. Rev.,
February 1, 2001;
22(1):
75 - 110.
[Abstract][Full Text]
S. Tsagarakis, C. Tsigos, V. Vassiliou, P. Tsiotra, H. Pratsinis, D. Kletsas, P. Trivizas, A. Nikou, T. Mavromatis, F. Sotsiou, et al. Food-Dependent Androgen and Cortisol Secretion by a Gastric Inhibitory Polypeptide-Receptor Expressive Adrenocortical Adenoma Leading to Hirsutism and Subclinical Cushing's Syndrome: In Vivo and in Vitro Studies
J. Clin. Endocrinol. Metab.,
February 1, 2001;
86(2):
583 - 589.
[Abstract][Full Text]
H. Mircescu, J. Jilwan, N. N'Diaye, I. Bourdeau, J. Tremblay, P. Hamet, and A. Lacroix Are Ectopic or Abnormal Membrane Hormone Receptors Frequently Present in Adrenal Cushing's Syndrome?
J. Clin. Endocrinol. Metab.,
October 1, 2000;
85(10):
3531 - 3536.
[Abstract][Full Text]
