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Functional and Nonfunctional Adrenocortical Tumors Demonstrate a High Responsiveness to Low-Dose Adrenocorticotropin

Division of Endocrinology (T.M., B.K., G.A.), Department of Internal Medicine, University of Ancona, 60100 Ancona, Italy; and Division of Endocrinology (F.M.), Department of Internal Medicine, University of Padua, 35100 Padua, Italy

Address all correspondence and requests for reprints to: Dr. Giorgio Arnaldi, Clinica di Endocrinologia, Azienda Ospedaliera Umberto I, Sede Torrette, 60100 Ancona, Italy. E-mail: arnaldi.giorgio{at}libero.it, g.arnaldi{at}ao-umbertoprimo.marche.it.

Aldosterone-producing adenomas (APAs) demonstrate exquisite sensitivity to endogenous ACTH. We previously showed an ACTH receptor overexpression in APAs compared with the other adrenal tumors.

To evaluate the meaning of such findings, we investigated the response of aldosterone, cortisol, and 17OH progesterone (17OHP) to 1 µg ACTH in 42 patients with adrenocortical tumors (23 NHAs, 9 APAs, and 10 CPAs) and 10 normal subjects (C). All 52 subjects were responsive to ACTH, and hormone peak levels were reached at 30 min. The aldosterone peak level was significantly higher in APAs [mean ± SEM: 84.3 ± 13.1 ng/dl (2335.1 ± 362.9 pmol/liter)] than in other tumors and control (C). Cortisol peak levels was higher in CPAs [37.1 ± 3.9 µg/dl (1023.9 ± 107.6 nmol/liter)] than in NHAs (P < 0.01), in C (P < 0.01) and in APAs (P = n.s.). 17OHP peak levels were significantly higher in patients with adrenocortical tumors toward C.

In summary: 1) low-dose ACTH induces an important stimulation in all tumors, suggesting preservation of high responsiveness to ACTH; 2) this is especially true for aldosterone in APA and could be of primary importance when performing diagnostic tests for hyperaldosteronism; and 3) 17OHP-hyperresponsiveness to low-dose ACTH is the most common alteration both in functional and nonfunctional tumors.

This work was partially supported by grant from Ministero dell’ Istruzione, dell’ Università e della Ricerca (Grant 200106 2719) and Associazione Italiana Ricerca sul Cancro (to F.M.).

Abbreviations: 17OHP, 17OH progesterone; APA, aldosterone-producing adenoma; AT, adrenocortical tumor; C, control; CPA, cortisol-producing adenoma; CT, computed tomography; HPA, hypothalamic-pituitary-adrenal; MRI, magnetic resonance imaging; NHA, nonhypersecreting adenoma; PRA, plasma renin activity.

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