Abnormalities of endocrine function in patients with clinically "silent" adrenal masses
Authors: Ambrosi Bruno , Peverelli Susanna , Passini Elena , Re Tiziana , Ferrario Riccardo , Colombo Paolo , Sartorio Alessandro , Faglia Giovanni 
Published: December 2008

Ambrosi B, Peverelli S, Passini E, Re T, Ferrario R, Colombo P, Sartorio A, Faglia G. Abnormalities of endocrine function in patients with clinically "silent" adrenal masses. Eur J Endocrinol 1995;132:422–8. ISSN 0804–4643
Because, in recent years, patients with incidentally discovered adrenal masses have been encountered increasingly, their endocrine function was investigated in basal conditions and after dynamic tests. Thirty-two patients (23 women and 9 men, aged 28–74 years) were studied. Lesion diameter, as documented by computed tomography and/or nuclear magnetic resonance imaging, ranged between 5 and 65 mm; the tumors were localized on the right in 22 patients, on the left in 5 and bilaterally in 5 cases. In basal conditions, urinary free cortisol (UFC) excretion, plasma adrenocorticotropin (ACTH) and cortisol levels were normal, except for 4 patients who showed high UFC and ACTH levels in the low–normal range. Ovine corticotropin-releasing hormone (CRH, 1 μg/kg iv) was given to 18 patients, inducing normal ACTH and cortisol responses in 12, blunted responses in 4 and no response in 2 cases. No reduction in ACTH and cortisol levels after suppression tests was observed in 4 of 29 patients after dexamethasone (1 mg overnight) or in 6 of 29 after loperamide. The 4 patients who were unresponsive to both tests did not show any further inhibition after high-dose dexamethasone administration, had low plasma ACTH levels and showed impaired or absent responses to the CRH test: they were diagnosed as affected with preclinical Cushing's syndrome. An exogenous ACTH test performed in 30 patients caused a normal cortisol rise. Basal mean 17-hydroxyprogesterone (17-OHP) levels were not different from those in normal subjects. After ACTH the 17-OHP rate increase was higher than in normal subjects (17-OHP(30–)/30 min = 0.31 ±0.04 vs 0.07 ± 0.01 nmol·1−1·min−1; mean±SEM, p < 0.01); in particular, this parameter was elevated in 18 of 30 patients (17-OHP(30–0)/30 min range = 0.23–1.07 vs 0.01–0.19 nmol·1−1·min−1 in normal subjects). In a subset of 11 patients, serum markers of bone (bone-GLA protein (BGP) and carboxyterminal cross-linked telopeptide of type I collagen (ICTP) and collagen turnover (aminoterminal propeptide of type III procollagen (PIIINP)) were significantly (p < 0.01) lower than in normal subjects: in particular, in 2 preclinical Cushing's patients they were markedly reduced and rose after unilateral adrenalectomy. Of these 2 patients who underwent surgery, 1 showed a secondary hypoadrenalism. The histological study in 7 operated patients revealed the presence of benign adenoma in 4 cases and carcinoma, myelolipoma and hematoma in the others. In conclusion, in patients with incidentalomas endocrine testing is recommended because about two-thirds of them show subtle signs of adrenal overactivity. In patients with enzymatic defects of steroidogenesis a surgical approach is not suggested. On the contrary, the existence of a preclinical Cushing's syndrome has to be investigated carefully and followed up in order to disclose the possible appearance of clinical and/or metabolic features induced by the hypercortisolism and to suggest a surgical treatment.
B Ambrosi, Institute of Endocrine Sciences, Ospedale Maggiore, IRCCS, via F Sforza 35, 20122 Milan, Italy