Evidence of 11 beta-hydroxylase deficiency in childhood adrenocortical tumors. The plasma corticosterone/11-deoxycorticosterone ratio as a possible marker for malignancy

Abstract

In search for a biochemical marker to differentiate between adrenocortical carcinoma (AC) and ade-noma (AA), plasma levels of the following steroids were studied preoperatively and postoperatively: 1 I-deoxycorticosterone (DOC), corticosterone (B), 11-deoxycortisol (S), and cortisol (F). Levels were measured by Sephadex LH-20 chromatography and specific radioimmunoassays. The subjects included eight children ages 2 years, 5 months to 9 years, 10 months. There were three girls and 5 boys with pseudoprecocious puberty due to adrenocortical tumors (histologically, four were AC and four, AA). The preoperative showed that DOC and S levels were elevated in all patients, F levels were elevated in four of eight children when compared with age-matched controls, whereas B was normal. Postoperatively, all levels returned to normal. The ratios of B/DOC and F/S as an index of adrenal I 1 beta-hydroxylase activity were calculated. The preoperative ratios of B/DOC were markedly decreased in all patients with AC compared to controls (7.7,4.1,5.9,1.9 versus 23.5, median), but normal in three of four patients with AA (16.2,29.6, 16.1). The F/S ratios were significantly lower in AC and AA when compared with controls. The data indicate a deficiency in 1 I beta-hydroxylation in cases of adrenocortical tumors. Despite a still limited number of patients, the decreased B/DOC ratios may possibly indicate malig-nancy and could be helpful in distinguishing by biochemical means between benign and malignant adrenocortical tumors.

Pseudohyperaldosteronism: Pathogenetic Mechanisms

“…133 In these syndromes the high concentrations of free DOC allows the binding of the steroid to renal MR with subsequent volume expansion, suppression of renin and aldosterone, and hypertension. [127][128][129][130][131][132][133][134][135][136][137][138] In patients with deficiency of 11β-hydroxylase the conversions of 11OH-cortisol to cortisol and of DOC to corticosterone are blocked, while concentrations of DOC and of adrenal androgens are elevated. Two different 11β-hydroxylases have been described: CYP11B1 is regulated by ACTH, is located in the zona fasciculata, and converts 11OH-cortisol to cortisol, the second is located in the zona glomerulosa (CVYP11B2) and converts DOC to corticosterone.…”

“…97,[115][116][117] Other factors must also be considered to explain why in some cases patients do not develop hypertension but only edema and hypokalemia. [117][118][119][120][121][122][123][124][125][126][127][128][129] The latter is not always present and many subjects are normokalemic. After withdrawal from the substance, the usually symptoms disappear within 2 weeks; however, hypertension may remain without a clinical picture of pseudohyperaldosteronism.…”

“…10,[128][129][130][131][132][133] The reduced or absent production of cortisol blocks the feedback regulation of ACTH, and, as a consequence, there is an increase in ACTH and in all the steroids that precede the blocked enzyme. 133 In these syndromes the high concentrations of free DOC allows the binding of the steroid to renal MR with subsequent volume expansion, suppression of renin and aldosterone, and hypertension.…”

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].…”

Primary Amenorrhea Accompanied by Adrenal Adenoma: Start of Menarche Soon after Tumor Resection.

“…Estradiol or androgen producing tumors have a high frequency of malignancy (1,12,17). Significantly higher baseline 1 1 -deoxycortisol/cortisol and 1 1 -deoxycorticosterone/corticosterone ratios, which were normalized after adrenalectomy, have been demonstrated in adrenocortical carcinomas (18). Pathological examination did not show any malignant histology at all in the present case.…”