The steroid metabolism exploration for the diagnosis of Connshing syndrome

Abstract

BACKGROUND: Reports of the synchronous glucocorticoid-mineralocorticoid activity in patients with Cushing’s syndrome and primary hyperaldosteronism have been found in the literature for fifty years, but there are few evidence-based studies on this issue.

AIM: To study mineralocorticoid and glucocorticoid secretion in patients with unilateral, bilateral tumours and bilateral hyperplasia of the adrenal cortex exploring urine and blood steroid metabolomes by chromatography methods.

MATERIALS AND METHODS: 114 patients with corticotrophin-independent Cushing’s syndrome, autonomous cortisol secretion and primary hyperaldosteronism were examined. The state of the pituitary-adrenal cortex system was assessed by classical methods of immunochemical analysis and functional tests. The corticosteroid metabolomics was studied in biological fluids using high-performance liquid chromatography and gas chromatography-mass spectrometry. In accordance with functional activities and type of hyperplasia, all the patients were divided into 8 subgroups: Cushing’s syndrome and corticosteroma (n = 19), Cushing’s syndrome and bilateral adenomas (n = 9), Cushing’s syndrome and bilateral macronodular hyperplasia (n = 8); autonomus cortisol secretion and unilateral adrenal adenoma (n = 19), autonomus cortisol secretion and bilateral adenomas (n = 14) and autonomus cortisol secretion with bilateral macronodular hyperplasia (n = 11); primary hyperaldosteronism with unilateral aldosteroneproducing adrenal adenoma (n = 15) and bilateral hyperplasia (n = 19). The group of healthy subjects was a control group (n = 22). Family hyperaldosteronism and adrenocortical cancer were excluded. Patients’ urinary corticosteroid excretion and blood steroid levels were compared using the nonparametric Mann–Whitney test.

RESULTS: Chromatographic methods have shown the presence of mineralocorticoid and glucocorticoid co-secretion in the patients with primary hyperaldosteronism: increased urine excretion of free cortisol 51 (27–90) ng/ml (p = 0.001) and its metabolite tetrahydrocortisol — 850 (720–994) μg/24 h (p = 0.0002) in the patients with Conn syndrome. As well as free cortisol 35 (32–72) µg/24 h (p = 0.002), tetrahydrocortisol — 1036 (490–1482) µg/24 h (p = 0.0049), 5α-tetrahydrocortisol — 1194 (411–1873) µg/24 h (p = 0.0048), 5α-tetrahydrocorticosterone — 339 (172–356) µg/24 h (p = 0.0008) in the patients with bilateral adrenal hyperplasia and hyperaldosteronism in comparison with the healthy persons. Glucocorticoid-mineralcorticoid activity was found among the patients with autonomous cortisol secretion and bilateral adrenal tumours: by increased levels of 18-hydroxycorticosterone in blood — 2.7 (1.3–3.5) ng/ml (p = 0.002). The patients with autonomous cortisol secretion and a single tumour had an increase of 18-hydroxycorticosterone in urine — 35 (33–55) µg/24 h (p = 0.0048) in comparison with the healthy subjects. The group of patients with corticotrophin-independent Cushing’s syndrome and unilateral corticosteroma was distinguished from the control group by high level of 18-hydroxycorticosterone in blood — 2.4 (1.0–4.3) ng/ml (p = 0.001) and urine — 42 (30–123) µg/24 h (p = 0.003).

CONCLUSIONS: Mixed glucocorticoid and mineralocorticoid activity of adrenal cortical tumor cells was revealed among the patients with Cushing’s syndrome, with autonomous cortisol secretion and primary hyperaldosteronism using chromatographic methods.

Keywords

Connshing’s syndrome / primary hyperaldosteronism / Cushing’s syndrome / high-performance liquid chromatography / gas chromatography-mass spectrometry

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