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Updated: May 5, 2026
A Novel Method: Super-selective Adrenal Venous Sampling
Published on: September 15, 2017
Intraadrenal corticotropin in bilateral macronodular adrenal hyperplasia
Estelle Louiset1, Céline Duparc, Jacques Young
1From INSERM Unité 982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, and Rouen University, Mont-Saint-Aignan (E.L., C.D., S.R., M.T.N., I.B., Z.B., J-.M.K., Y.A., H.L.), the Department of Endocrinology, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris (AP-HP), University Paris Sud, INSERM Unité 693, Le Kremlin-Bicêtre (J.Y.), INSERM Unité 1016, Institut Cochin (R.L., L.G., X.B., J.B.), the Department of Endocrinology AP-HP, Hôpital Cochin (L.G., X.B., J.B.), Université Paris Descartes (L.G., X.B., J.B.), Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104 (L.G., X.B., J.B.), and the Department of Endocrinology, Hôpital Saint-Antoine, AP-HP (S.C.-M.), Paris; the Department of Endocrinology and Metabolic Diseases, Centre Hospitalier Universitaire Larrey, Toulouse (P.C.); the Department of Endocrinology, Hôpital Haut Lévêque, Centre Hospitalier Universitaire de Bordeaux, Pessac (A.T.); Service de Médecine Interne et Nutrition, Centre Hospitalier Régional Universitaire de Strasbourg, Strasbourg (F.G.); and the Department of Endocrinology, Diabetes, and Metabolic Diseases, Rouen University Hospital, Rouen (J.M.K., H.L.) - all in France.
Background:
Bilateral macronodular adrenal hyperplasia is a rare cause of primary adrenal Cushing's syndrome. In this form of hyperplasia, hypersecretion of cortisol suppresses the release of corticotropin by pituitary corticotrophs, which results in low plasma corticotropin levels. Thus, the disease has been termed corticotropin-independent macronodular adrenal hyperplasia. We examined the abnormal production of corticotropin in these hyperplastic adrenal glands.
Methods:
We obtained specimens of hyperplastic macronodular adrenal tissue from 30 patients with primary adrenal disease. The corticotropin precursor proopiomelanocortin and corticotropin expression were assessed by means of a polymerase-chain-reaction assay and immunohistochemical analysis. The production of corticotropin and cortisol was assessed in 11 specimens with the use of incubated explants and cell cultures coupled with hormone assays. Corticotropin levels were measured in adrenal and peripheral venous blood samples from 2 patients.
Results:
The expression of proopiomelanocortin messenger RNA (mRNA) was detected in all samples of hyperplastic adrenal tissue. Corticotropin was detected in steroidogenic cells arranged in clusters that were disseminated throughout the adrenal specimens. Adrenal corticotropin levels were higher in adrenal venous blood samples than in peripheral venous samples, a finding that was consistent with local production of the peptide within the hyperplastic adrenals. The release of adrenal corticotropin was stimulated by ligands of aberrant membrane receptors but not by corticotropin-releasing hormone or dexamethasone. A semiquantitative score for corticotropin immunostaining in the samples correlated with basal plasma cortisol levels. Corticotropin-receptor antagonists significantly inhibited in vitro cortisol secretion.
Conclusions:
Cortisol secretion by the adrenals in patients with macronodular hyperplasia and Cushing's syndrome appears to be regulated by corticotropin, which is produced by a subpopulation of steroidogenic cells in the hyperplastic adrenals. Thus, the hypercortisolism associated with bilateral macronodular adrenal hyperplasia appears to be corticotropin-dependent. (Funded by the Agence Nationale de la Recherche and others.).
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