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Adrenal Sensitivity to Adrenocorticotropin 1–24 Is Reduced in Patients with Autoimmune Polyglandular Syndrome

Division of Endocrinology (R.G., M.P., S.O., M.Bald., M.Balb., E.G., E.A.), Department of Internal Medicine, University of Turin, Turin, Italy; and Department of Internal Medicine (S.L., A.F.), University of Perugia, Perugia, Italy

Address all correspondence and requests for reprints to: Emanuela Arvat, M.D., Divisione di Endocrinologia, Ospedale Molinette, C.so Dogliotti 14, 10126 Torino, Italy. E-mail: emanuela.arvat{at}unito.it.

Autoimmune polyglandular syndromes are fairly common diseases that are classified into four constellations based on the clinical clustering of the various component diseases. In types 1, 2, and 4, primary adrenal insufficiency due to an autoimmune process is usually present, but its diagnosis is often delayed because it is difficult to detect in a subclinical phase. It is widely accepted that the classical dose of 250 µg ACTH_1–24 is supramaximal, whereas 0.06 µg has been shown to be one of the lowest ACTH doses that is able to stimulate adrenal secretion in normal young subjects. The aim of this study was to clarify the sensitivity and maximal secretory response of the adrenal gland to ACTH in a group of patients with at least two autoimmune diseases, without clinical signs and symptoms of overt or subclinical hypocortisolism. Cortisol (F), aldosterone (A), and dehydroepiandrosterone (DHEA) responses to the sequential administration of very low and supramaximal ACTH_1–24 doses [0.06 µg followed by 250 µg ACTH_1–24 iv at 0 and +60 min] were studied in 18 patients with at least two autoimmune diseases (AP; age, 20–40 yr; body mass index, 22–26 kg/m²). The results in the patients were compared with the results recorded in 12 normal age-matched control subjects (CS; age, 22–34 yr; body mass index, 20–25 kg/m²). At baseline, ACTH levels in AP were within the normal range but higher (P < 0.05) than in CS, whereas F, A, DHEA, urinary-free F, and plasma renin activity were similar in both groups. F, A, and DHEA responses to ACTH were dose dependent in both groups. However, in AP, F, A, and DHEA levels showed no response to the 0.06-µg ACTH dose, which, in turn, elicited clear responses (P < 0.01) in CS. On the other hand, F, A, and DHEA responses to 250 µg ACTH in AP were not different from those in CS. In conclusion, patients with autoimmune diseases who displayed a normal basal adrenal function showed a loss of F, A, and DHEA response to the very low ACTH dose, although they were normal responders to the high ACTH dose. These data are likely to indicate that a reduced sensitivity to ACTH in all adrenal zones occurs in patients with different types of autoimmune disease.

This work was supported by the University of Turin, the Foundation for the Study of Endocrine and Metabolic Diseases, and Ministry of University and Scientific Research Grant PRIN 2001063439.

Abbreviations: A, Aldosterone; AP, autoimmune disease patients; APS, autoimmune polyglandular syndromes; CS, control subjects; DHEA, dehydroepiandrosterone; F, cortisol; 21OHAb, 21-hydroxylase autoantibody; PRA, plasma renin activity; UFC, urinary-free cortisol.

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