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Background Urinary 18-hydroxycortisol has been investigated as a marker of aldosterone-producing adenoma (APA). The aim of this study was to develop and validate a method for the measurement of 18-hydroxycortisol using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Methods Urine was collected over a 24-hour period in patients with APA ( n = 11), idiopathic hyperaldosteronism (IHA, n = 9), and essential hypertension (EH, n = 6). 18-Hydroxycortisol was extracted in solid-phase, and measured by LC-MS/MS based on selected reaction monitoring. Results The method allowed quantification of 18-hydroxycortisol with a lower quantification limit of 0.26 nmol/L, intra- and inter-assay coefficients of variation of Conclusions The proposed method met the basic analytical requirements and was considered to be useful in the screening and differential diagnosis of APA.

Plasma aldosterone concentration/plasma renin activity ratio is widely used as a screening tool of primary aldosteronism (PA). We evaluated that plasma aldosterone concentration (pg/ml)/plasma active renin concentration (pg/ml) ratio >40 is useful for screening of PA among hypertensive patients. Subsequently, oral sodium loading test (10-12g NaCl for 3 days) is performed to the suspected PA patients and definite diagnosis of PA is made if 24-hr urinary aldosterone is more than 13-15 μg/day on the third day. In addition, furosemide loading test is also shown to be useful to make definite diagnosis of PA if plasma active renin concentration is still suppressed after 2 hr of furosemide administration. Subsequently, differential diagnosis whether unilateral or bilateral lesions should be determined in definite PA patients. If unilateral lesion is suspected by adrenal CT scan, ^I-adosterol adrenal scintigraphy should be performed. If adosterol is accumulated in the adrenal tumor detected by CT scan, laparoscopic unilateral adrenalectomy should be indicated without performing adrenal venous sampling (AVS). However, if adosterol scintigraphy shows other findings, such as bilateral or contralateral accumulation, ACTH-loading AVS should be performed to determine laterality of aldosterone production. Besides, when 24-hr urinary 18-hydroxycortisol (18-OH-F) is more than 0.2 mg/gCr, diagnosis of aldosterone-producing adenoma is indicated. When AVS is performed, hormonal laterality should be determined by aldosterone/cortisol (A/C) ratio in the adrenal veins and inferior vena cava. Lateralized ratio is calculated by A/C ratio of the tumor side-adrenal vein/A/C ratio of the nontumor side-adrenal vein. Contralateral ratio is calculated by A/C ratio of nontumor side-adrenal vein/A/C ratio of the inferior vena cava. Unilateral legion is indicated upon lateralized ratio >4 and/or contralateral ratio

A method for the determination of urinary 18-hydroxycortisol by high-performance liquid chromatography is described. Urinary samples were first mixed with an internal standard, 18-hydroxyprednisolone. 18-Hydroxycortisol and 18-hydroxyprednisolone, extracted by a Bond Elut column, were dehydrated by 1% (w/v) p-toluenesulphonic acid to the 11,18-epoxides. The epoxides were separated into two distinct peaks on a Resolve Silica column with a mobile phase of chloroform-methanol (100:2.5, v/v). The detection wavelength was 248 nm. The urinary 18-hydroxycortisol concentration was calculated from peak-height ratio of 11,18-epoxycortisol to 11,18-epoxyprednisolone. The linearity of the ratio was satisfactory in the range 12.5-300 ng per injection of 11,18-epoxycortisol. A specific increase of urinary 18-hydroxycortisol in patients with primary aldosteronism was demonstrated.

SUMMARY We report a newly diagnosed family in which a father and his two sons were found to be hypertensive and to have the rare familial condition dexametha-sone-suppressible hyperaldosteronism (DSH). All three patients became normotensive on dexamethasone treatment alone and have been successfully maintained on low doses of the drug for 6 months since diagnosis. Each of the patients had extremely high plasma and urinary concentrations of the recently discovered steroid 18-hydroxycortisol, which were more than ten times higher than the upper normal limit. Plasma levels were readily suppressed by dexamethasone treatment. The hypothesis that 18-hydroxycortisol might derive from 18-hydroxylation of recirculating Cortisol was tested by measuring plasma 18-hydroxycortisol levels during low-dose and high-dose hydrocortisone infusions, in a normal subject and in one of the patients with DSH. During the high-dose infusions (with plasma Cortisol levels of 3000-5000 nmol/1) there was net production of 18-hydroxycortisol within 8 h, but this was not observed during the low-dose infusions (plasma Cortisol levels 300-400 nmol/1). The origin of 18-hydroxycortisol remains uncertain: these findings do not support the recirculation theory, but lend weight to the alternative hypothesis that 18-hydroxycortisol is produced in transitional adrenocortical tissue. This steroid is of considerable value in the differential diagnosis of primary hyperaldosteronism and may also be important as a marker of transitional adrenal cell function.