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Factors Controlling the Biosynthesis of Aldosterone
Published in Ronald Hobkirk, Steroid Biochemistry, 1979
Aldosterone possesses an aldehyde group on angular carbon-18. It is not yet completely clear whether aldosterone is derived directly from corticosterone or indirectly with 18-hydroxycorticosterone as an intermediary. The mitochondrial oxygenation at position 18 of corticosterone is dependent on the presence of molecular oxygen and NADPH: this reaction can also be inhibited in the presence of carbon monoxide.46,47 The transformation of 18-hydroxycorticosterone to aldosterone in vitro by adrenocortical tissue was shown possible although the yield is small compared to that from corticosterone under the same conditions.48,49 Sandor et al.47 reported no transformation of exogenous 18-hydroxycorticosterone to aldosterone by duck adrenal; results of their kinetic studies suggest that aldosterone and 18-hydroxycorticosterone originate simultaneously from corticosterone. It is interesting to note that, in all the species studied, adrenal aldosterone biosynthesis is always accompanied by that of 18-hydroxycorticosterone. In solution, 18-hydroxycorticosterone is in the cyclic 18,20 hemiketal form; this species is more resistant to oxidation than the open α-ketol and may be also more resistant to dehydrogenation. Consequently, we have to be careful in interpreting low aldosterone formation yield when 18-hydroxycorticosterone is used as substrate in vitro; it is quite possible that in vivo conditions might differ considerably and be much more propitious to the dehydrogenation of 18-hydroxycorticosterone.
Liddle syndrome misdiagnosed as primary aldosteronism is caused by inaccurate aldosterone-rennin detection while a novel SCNN1G mutation is discovered
Published in Blood Pressure, 2022
Yaling Yang, Chenwei Wu, Duoduo Qu, Xinyue Xu, Lili Chen, Quanya Sun, Xiaolong Zhao
Chemiluminescence detection is based on antigen-antibody reaction. Some substances with similar molecular weights and/or structures to aldosterone might interfere with the detection such as prednisolone, hydrocortisone, cortisone, 17 deoxycortisol and 18 hydroxycorticosterone [9]. When plasma aldosterone is detected using the chemiluminescence method, the obtained value is usually higher than the actual value, especially when the plasma aldosterone concentrations are less than 7.2 ng/dl and the deviations usually are 50%–100% higher than the actual values [6,10]. The underlying reason might be the cross-reaction between aldosterone antibody and antigen such as aldosterone structural analogues and/or aldosterone metabolites [9]. At present, there are several manufacturers providing chemiluminescent aldosterone test kits including Italy Diasorin, Zhengzhou Antu, Shenzhen Mindray, Changchun Dirui, Tianjin Boasais, Shenzhen New industry, etc in China. The results of the quality assessment of aldosterone in 2019 from 272 clinical laboratories in China showed that the mass spectrometry method was the most accurate, followed by the Italy Diasorin test kit; Other chemiluminescence methods had large deviations, which are usually negatively correlated with the sample concentration and the system deviation could be as high as 479% [6,10].
A precise, sensitive and stable LC-MSMS method for detection of picomolar levels of serum aldosterone
Published in Scandinavian Journal of Clinical and Laboratory Investigation, 2018
Margrete Lie, Ketil Thorstensen
During validation of the method, we observed baseline separation between aldosterone and prednisolone, cortisone, prednisone and 18-hydroxycorticosterone, which were the most obvious sources of possible interference. Prednisolone and cortisone has a mass-to-charge ratio (m/z) identical to aldosterone. Prednisone does not have the same m/z as aldosterone, but with its mass-to-charge ratio (m/z) of 359 (in positive mode), its natural C14-isotope (M + 2) has the same m/z as aldosterone and may interfere. Possible interference of 18-hydroxycorticosterone in ESI negative mode has been reported [4]. Since this is an endogenous compound that will be present in all patient samples it is important to exclude. Although 18-hydroxycorticosterone has an m/z of 363 (aldosterone M +2), nevertheless we observed that 18-hydroxycorticosterone produces the same transitions as aldosterone (361 > 315 and 361 > 343) but with a different qualifier ratio and retention time. We acknowledge that there will always be a possibility for interference from other drugs (or food) and their metabolites. Since there are no way to test for all metabolites, the importance of using qualifiers and routinely monitoring qualifier ratios, is obvious.