Coexistence of 21-Hydroxylase and 11β-Hydroxylase Deficiency in Adrenal Incidentalomas and in Subclinical Cushing’s Syndrome

Abstract

Objective: The prevalence of steroid secretion abnormalities was studied by evaluating the 17-hydroxyprogesterone (17-OHP) and 11-deoxycortisol (S) responses to adrenocorticotropic hormone (ACTH) stimulation in 48 patients with ‘nonfunctioning’ incidentalomas and in 10 patients with ‘subclinical’ Cushing’s syndrome. Methods: In all patients the cortisol, 17-OHP, and S levels were measured after ACTH test. Eight patients were reinvestigated after surgery. Results: In patients with nonfunctioning lesions, the ACTH test induced 17-OHP and S peaks higher than in normals (p < 0.005). In 10 cases an augmented rise of 17-OHP and S was observed. In patients with subclinical Cushing’s syndrome, the 17-OHP peak after ACTH was greater than in patients with nonfunctioning lesions and in normals (p < 0.005); the S peak was also higher than in controls (p < 0.005). In 7 of 8 operated patients, the exaggerated 17-OHP peak was normalized. Conclusions: A combined impairment of different enzyme activities is frequently present in adrenal incidentalomas; the alteration of enzymatic pathways can also coexist with the presence of partial cortisol autonomy.

A unique case of a benign adrenocortical tumor with triple secretion of cortisol, androgens, and aldosterone. Development of multiple sclerosis after surgical removal of the tumor

“…[9][10][11][12][13] In our case reduced activity of 21-hydroxylase within the tumor (normal 17OHP levels after tumor excision) could account for the exaggerated response of 17OHP to ACTH, and the increased testosterone, and Ä 4Á levels. Similar overresponse of 17OHP to ACTH has been described before in ten patients with sub-clinical Cushings syndrome, 14 showing that alterations in enzymatic pathways can coexist with the presence of cortisol autonomy. Co-secretion of cortisol and androgens (elevated DHEAS, Ä 4Á , and testosterone) has also been described in six cases of adrenal tumors where there was no evidence of malignancy.…”

Clinical perspectives in congenital adrenal hyperplasia due to 11β-hydroxylase deficiency

“…However, this metaanalysis only included studies with 21OHD. Impaired 11β-hydroxylation activity has been demonstrated in functional adrenocortical tumors and non-functional adrenal incidentalomas based on in-vitro enzymatic analyses or ACTH stimulation test [158][159][160][161]. Bilateral giant adrenal incidentalomas have been reported in a 22-year-old man who after investigations turned out to have 11βOHD and the karyotype was 46XX [162].…”

Late-onset Congenital Adrenal Hyperplasia with Cushing Syndrome

“…Among the participants of that study, the 17-OH P levels declined to normal levels in seven of eight patients treated with surgery. In addition, the adrenal incidentaloma patients exhibited enzymatic diversity with alterations in enzymatic pathways being a phenomenon mostly associated with glucocorticoid autonomy (24). The results of that study showed that the possible effects of changes in steroideogenetic pathways on adrenocortical tumor formation can be documented using molecular analysis.…”

“…A decade ago, researchers suggested that adrenal tumors are capable of changing their enzymatic activity (24). Previously, 21-hydroxylase and 11 beta hydroxylase deficiencies were explored in a study consisting of 48 cases of adrenal incidentaloma and 10 cases of subclinical CS (24).…”

“…Previously, 21-hydroxylase and 11 beta hydroxylase deficiencies were explored in a study consisting of 48 cases of adrenal incidentaloma and 10 cases of subclinical CS (24). In that study, the results of ACTH stimulation tests showed an exaggerated response in adrenal incidentaloma cases, in which the increase in the 17-OH P and 11 deoxycortisol levels was significantly higher in the subclinical CS patients (24). Among the participants of that study, the 17-OH P levels declined to normal levels in seven of eight patients treated with surgery.…”