Urinary Tetrahydroaldosterone Research Articles

Urinary tetrahydroaldosterone is associated with circulating FGF23 in kidney stone formers

The spectrum of diseases with overactive renin–angiotensin–aldosterone system (RAS) or elevated circulating FGF23 overlaps, but the relationship between aldosterone and FGF23 remains unclarified. Here, we report that systemic RAS activation sensitively assessed by urinary tetrahydroaldosterone excretion is associated with circulating C-terminal FGF23. We performed a retrospective analysis in the Bern Kidney Stone Registry, a single-center observational cohort of kidney stone formers. Urinary excretion of the main aldosterone metabolite tetrahydroaldosterone was measured by gas chromatography–mass spectrometry. Plasma FGF23 concentrations were measured using a C-terminal assay. Regression models were calculated to assess the association of plasma FGF23 with 24 h urinary tetrahydroaldosterone excretion. We included 625 participants in the analysis. Mean age was 47 ± 14 years and 71% were male. Mean estimated GFR was 94 ml/min per 1.73 m2. In unadjusted analyses, we found a positive association between plasma FGF23 and 24 h urinary tetrahydroaldosterone excretion (β: 0.0027; p = 4.2 × 10–7). In multivariable regression models adjusting for age, sex, body mass index and GFR, this association remained robust (β: 0.0022; p = 2.1 × 10–5). Mineralotropic hormones, 24 h urinary sodium and potassium excretion as surrogates for sodium and potassium intake or antihypertensive drugs did not affect this association. Our data reveal a robust association of RAS activity with circulating FGF23 levels in kidney stone formers. These findings are in line with previous studies in rodents and suggest a physiological link between RAS system activation and FGF23 secretion.

Responses of the renin-angiotensin-aldosterone system in pregnant chronic kidney disease patients with and without superimposed pre-eclampsia.

BackgroundWomen with chronic kidney disease (CKD) are at increased risk of superimposed pre-eclampsia (SPE). Accurate identification of SPE is challenging. We hypothesized that specific components of the renin–angiotensin–aldosterone system (RAAS) would discriminate between CKD and SPE. The aim of the study was to establish differences in circulating and intrarenal RAAS in women with CKD with and without SPE and compare these to normotensive controls (NCs) and women with pre-eclampsia (PE).MethodsWhite European NC women (n = 20), women with PE (n = 9), normotensive CKD without SPE (n = 8) and with SPE (n = 11) were recruited in the third trimester. Plasma renin, plasma and urine total angiotensinogen (AGT) concentrations were quantified by enzyme-linked immunosorbent assay, urinary tetrahydroaldosterone (TH-aldo) concentration by gas chromatography-mass spectrometry and placental growth factor (PlGF) by immunoassay.ResultsUrinary TH-aldo:creatinine ratios were lower in women with PE or SPE compared with NC or women with CKD (P < 0.05 for all). The same group differences were observed for plasma active renin and PlGF concentrations (P < 0.05 for all). Urine total AGT was higher in women with PE compared with NC (P < 0.05) and urine TH-aldo:urine AGT was lower (P < 0.05). However, women with SPE had lower urinary AGT concentrations compared with women with PE (P < 0.05). No differences in plasma total AGT were observed between groups.ConclusionsWomen with SPE have a lower urinary TH-aldo:creatinine ratio, lower plasma active renin and lower PlGF concentrations than women with CKD, comparable to women with PE without pre-existing disease, suggestive of similar pathophysiology. These data suggest disruption of the RAAS pathway in SPE similar to PE. Exploration of the predictive value of RAAS components for adverse pregnancy events in women with CKD is required.

PP.23.04] RESPONSES OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM TO PLASMA VOLUME DEPLETION IN PRE-ECLAMPSIA &amp; SUPERIMPOSED PRE-ECLAMPSIA

Objective: Women with chronic kidney disease (CKD) are at increased risk of superimposed pre-eclampsia (SPE) and associated adverse pregnancy outcomes. Diagnosis of SPE using blood pressure and proteinuria is of limited use because these may develop in women with CKD even without the condition. Inaccurate diagnosis may result in unnecessary iatrogenic preterm delivery. Plasma and urinary aldosterone concentrations are elevated in patients with CKD, but suppressed in established pre-eclampsia (PE). The aim of the study was to determine plasma active renin, total plasma and urinary angiotensinogen (AGT) and aldosterone availability in women with CKD with and without SPE compared with normotensive controls (NC) and those with PE without CKD. Design and method: NC women (n = 19), women with PE (n = 14), CKD without SPE (n = 6) and with SPE (n = 11) were recruited from two tertiary antenatal clinics (mean ± SD 38 ± 3 weeks). Active renin and total AGT concentrations were measured by ELISA; urinary tetrahydroaldosterone was measured by gas chromatography-mass spectrometry; creatinine was measured using a standard clinical laboratory assay for normalisation. Results: Aldosterone and plasma active renin (Kruskal Wallis, both P < 0.05) were significantly different between groups. Aldosterone: creatinine ratios were significantly lower in both PE and SPE compared to the NC and women with CKD (median [IQR], PE: 6.5 [3, 14.4]; SPE: 10.8 [5.4, 16.4]; NC: 13.8 [9.1, 29.8]; CKD: 24.2 [16.3, 37.9] μg/mmol creatinine; P < 0.05 for all). Plasma active renin concentrations were also lower in PE, SPE and CKD women compared to NC women (PE: 5.3 [9.7, 21.8]; SPE: 3.4 [2.4, 12]; CKD: 3.9 [3.2, 6.2]; NC: 5.3 [0.2, 8.7] pg/ml; P < 0.05 for all). No differences in either plasma or urinary total AGT were observed between the groups. Conclusions: Women with SPE have lower urinary aldosterone and plasma active renin than women with CKD in keeping with women with PE without pre-existing kidney disease, suggestive of similar pathophysiology. Further exploration of the predictive value of low urinary aldosterone and plasma renin for adverse pregnancy events in women with CKD and its role in cases of diagnostic uncertainty is required.

Placental expression of the angiogenic placental growth factor is stimulated by both aldosterone and simulated starvation

Aldosterone is an important factor supporting placental growth and fetal development. Recently, expression of placental growth factor (PlGF) has been observed in response to aldosterone exposure in different models of atherosclerosis. Thus, we hypothesized that aldosterone up-regulates growth-adaptive angiogenesis in pregnancy, via increased placental PlGF expression.We followed normotensive pregnant women (n = 24) throughout pregnancy and confirmed these results in a second independent first trimester cohort (n = 36). Urinary tetrahydroaldosterone was measured by gas chromatography-mass spectrometry and corrected for creatinine. Circulating PlGF concentrations were determined by ELISA. Additionally, cultured cell lines, adrenocortical H295R and choriocarcinoma BeWo cells, as well as primary human third trimester trophoblasts were tested in vitro. PlGF serum concentrations positively correlated with urinary tetrahydroaldosterone corrected for creatinine in these two independent cohorts. This observation was not due to PlGF, which did not induce aldosterone production in cultured H295R cells. On the other hand, PlGF expression was specifically enhanced by aldosterone in the presence of forskolin (p < 0.01) in trophoblasts. A pronounced stimulation of PlGF expression was observed with reduced glucose concentrations simulating starvation (p < 0.001).In conclusion, aldosterone stimulates placental PlGF production, enhancing its availability during human pregnancy, a response amplified by reduced glucose supply. Given the crucial role of PlGF in maintaining a healthy pregnancy, these data support a key role of aldosterone for a healthy pregnancy outcome.

Classic and non-classic 21-hydroxylase deficiency can be discriminated from P450 oxidoreductase deficiency in Japanese infants by urinary steroid metabolites.

.We previously reported a two-step biochemical diagnosis to discriminate classic 21-hydroxylase deficiency (C21OHD) from P450 oxidoreductase deficiency (PORD) by using urinary steroid metabolites: the pregnanetriolone/tetrahydrocortisone ratio (Ptl / the cortisol metabolites 5α- and 5β-tetrahydrocortisone (sum of these metabolites termed THEs), and 11β-hydroxyandrosterone (11OHAn). The objective of this study was to investigate whether both C21OHD and non-classic 21OHD (C+NC21OHD) could be biochemically differentiated from PORD. We recruited 55 infants with C21OHD, 8 with NC21OHD, 16 with PORD, 57 with transient hyper-17α-hydroxyprogesteronemia (TH17OHP), and 2,473 controls. All infants were Japanese with ages between 0–180 d. In addition to Ptl, THEs, and 11OHAn, we measured urinary tetrahydroaldosterone (THAldo) and pregnenediol (PD5). The first step: by Ptl with the age-specific cutoffs 0.06 mg/g creatinine (0–10 d of age) and 0.3 mg/g creatinine (11–180 d of age), we were able to differentiate C+NC21OHD and PORD from TH17OHP and controls (0–10 d of age: 0.065–31 vs. < 0.001–0.052, 11–180 d of age: 0.40–42 vs. < 0.001–0.086) with 100% sensitivity and specificity. The second step: by the 11OHAn/THAldo or 11OHAn/PD5 ratio with a cutoff of 0.80 or 1.0, we were able to discriminate between C+NC21OHD and PORD (1.0–720 vs. 0.021–0.61 or 1.8–160 vs. 0.005–0.32, respectively) with 100% sensitivity and specificity. Ptl, 11OHAn/THAldo, and 11OHAn/PD5 could differentiate between C+NC21OHD and PORD in Japanese infants.

Systemic availability of placental growth factor correlates with urinary tetrahydroaldosterone excretion in normal and preeclamptic pregnancy

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Normotensive Blood Pressure in Pregnancy

A successful pregnancy requires an accommodating environment. Salt and water availability are critical for plasma volume expansion. Any changes in sodium intake would alter aldosterone, a hormone previously described beneficial in pregnancy. To date, it remains ambiguous whether high aldosterone or high salt intake is preferable. We hypothesized that increased aldosterone is a rescue mechanism and appropriate salt availability is equally effective in maintaining a normotensive blood pressure (BP) phenotype in pregnancy. We compared normotensive pregnant women (n=31) throughout pregnancy with young healthy female individuals (n=31–62) and performed salt sensitivity testing within the first trimester. Suppression of urinary tetrahydro-aldosterone levels by salt intake as measured by gas chromatography–mass spectrometry and urinary sodium excretion corrected for creatinine, respectively, was shifted toward a higher salt intake in pregnancy ( P &lt;0.0001). In pregnancy, neither high urinary tetrahydro-aldosterone nor sodium excretion was correlated with higher BP. In contrast, in nonpregnant women, systolic BP rose with aldosterone ( P &lt;0.05). Testing the impact of salt on BP, we performed salt sensitivity testing in a final cohort of 19 pregnant and 24 nonpregnant women. On salt loading, 24-hour mean arterial pressure rose by 3.6±1.5 and dropped by –2.8±1.5 mm Hg favoring pregnant women ( P &lt;0.01; χ 2 =6.04; P &lt;0.02). Our data suggest first that salt responsiveness of aldosterone is alleviated in conditions of pregnancy without causing aldosterone-induced hypertension. Second, salt seems to aid in BP lowering in pregnancy for reasons incompletely elucidated, yet involving renin suppression and potentially placental sensing mechanisms. Further research should identify susceptible individuals and clarify effector mechanisms.

Urinary sodium excretion is the main determinant of mineralocorticoid excretion rates in patients with chronic kidney disease

Blockade of the mineralocorticoid receptor (MR) in patients with chronic kidney disease (CKD) improves surrogate cardiovascular outcomes, such as left ventricular mass. Animal models of renal disease support a pathological role of mineralocorticoids, in the context of a high sodium intake. We aimed to assess the regulation of mineralocorticoid biosynthesis in patients with CKD. Seventy patients with CKD stages 3/4 and 30 patients with essential hypertension (EH) were recruited. Patients underwent detailed clinical phenotyping, drug history and biochemical assessment. Patients completed a 24-h urine collection for measurement of urinary tetrahydroaldosterone (THALDO) and tetrahydrocorticosterone (THDOC) excretion rates (measured using gas chromatography-mass spectrometry) and urinary electrolytes. The factors which correlated significantly with THALDO and THDOC excretion were entered into linear regression models. Patients with EH and CKD were well matched with no significant differences in gender, age or weight. The mean estimated glomerular filtration rate (eGFR) in CKD patients was 38.6/min/1.73 m(2). The mean urinary excretion rates of THALDO, THDOC and 24-h urinary sodium (24-h USod) were not significantly different between CKD and EH patients. The level of renal function did not correlate with THALDO or THDOC excretion. In patients with CKD, 24-h USodium (r = 0.614, P < 0.001) and 24-h UPotassium (r = 0.538, P < 0.001) were positively correlated with THALDO excretion. On multivariate linear regression analysis, 24-h USod was the strongest independent predictor (P = 0.004) of THALDO and THDOC excretion in CKD. In patients with EH, no relationship was seen between mineralocorticoid excretion and 24-h urinary sodium excretion. In patients with CKD, 24-h urinary sodium excretion is the strongest positive predictor of urinary mineralocorticoid excretion. The nature of this relationship is unexpected, novel, not seen in patients with EH and may explain the association seen between high urinary sodium excretion, mineralocorticoids and poor outcomes in patients with CKD.

Indicators of mineralocorticoid excess in the evaluation of primary aldosteronism

It is suggested to use the aldosterone-to-renin ratio (ARR) as a first test in the screening for primary aldosteronism (PA). However, many groups rather rely on the determination of urinary tetrahydroaldosterone secretion; others calculate a ratio of urinary aldosterone to plasma renin activity. The aim of the present study was to evaluate the usefulness of different parameters of aldosterone excess in the case finding of PA. The study included 28 patients with PA and 33 subjects with essential hypertension. Clinical data, which included the hormonal parameters, serum aldosterone, plasma renin concentration, urinary free aldosterone and metabolites and serum and urinary electrolyte levels were analyzed. These indices of aldosterone excess, the ARR, serum sodium to urinary sodium to (serum potassium)(2) to urinary potassium (SUSPPUP) ratio and combinations of these parameters were compared between the groups. Receiver-operating curve analysis revealed that the ARR multiplied by the SUSPPUP ratio (ARR x SUSPPUP) is the most reliable screening test, with a sensitivity of 92.3% and a specificity of 93.9% (cutoff point 199.2 (mmol l(-1))(-1)). The combination of ARR x SUSPPUP ratio with urinary free aldosterone divided by the plasma renin concentration rendered a specificity of 100%. Less useful was the correction of urinary free aldosterone and its metabolites for sodium excretion. Although the ARR and urinary free aldosterone divided by renin are good tests in the screening for PA, the combination of ARR with SUSPPUP ratio is a better indicator of an aldosterone excess and aldosterone action in patients with ongoing antihypertensive medication. Antihypertensive drugs only marginally interfere with the SUSPPUP ratio, but they may influence the ARR, whereby the effects in PA patients seem to be negligible.

Association between Aldosterone Production and Variation in the 11β-Hydroxylase (CYP11B1) Gene

Variation in the region of chromosome 8 including the genes steroid 11beta-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) influences mineralocorticoid and glucocorticoid metabolism. However, the relative importance of polymorphisms in CYP11B1 and CYP11B2 in determining these phenotypes is unknown. Our objective was to investigate genetic influences of the CYP11B1 and CYP11B2 genes on mineralocorticoid metabolism. We measured 24-h urinary excretion of the key metabolites of the principal mineralocorticoids, glucocorticoids and androgens secreted by the adrenal cortex. We genotyped polymorphisms spanning the CYP11B1 and CYP11B2 genes, which together capture all common variations at the locus. Participants included 573 members of 105 British Caucasian families ascertained on a hypertensive proband. We assessed heritability of urinary tetrahydroaldosterone (THAldo) excretion and association of THAldo excretion with genotype. The heritability of THAldo excretion was 52% (P < 10(-6)). There was significant association between THAldo and genotype at several of the CYP11B1/B2 polymorphisms. The strongest association was observed at the rs6387 (2803A/G) polymorphism in intron 3 of CYP11B1 (P = 0.0004). Association followed a codominant model with a 21% higher THAldo excretion per G allele. Genotype at rs6387 accounted for 2.1% of the total population variability of THAldo. We found significant association between THAldo excretion and urinary total androgen excretion, urinary tetrahydrodeoxycortisol level, and urinary cortisol metabolites (all P < 0.001). Aldosterone synthesis is highly heritable and is affected by genotype at CYP11B1. Our findings support the hypothesis that genetically determined differences in 11-hydroxylation efficiency can have downstream effects on mineralocorticoid synthesis. Such effects may be of relevance to the development of low-renin essential hypertension.

Confirmatory testing in normokalaemic primary aldosteronism: the value of the saline infusion test and urinary aldosterone metabolites

Primary aldosteronism has recently been recognized as the most frequent cause of secondary hypertension. Since most patients are normokalaemic, differentiation to essential hypertension is challenging. As differentiation by baseline aldosterone/renin ratio may be insufficient, diagnosis should be confirmed by additional tests. However, as most confirmatory tests have been evaluated in hypokalaemic primary aldosteronism only, we reassessed the value of the saline infusion test and 24 h urinary aldosterone metabolites as confirmatory tests for both normo- and hypokalaemic primary aldosteronism under current antihypertensive medication. 25 patients with primary aldosteronism (11 hypokalaemic, 14 normokalaemic), 29 patients with essential hypertension and 47 normotensive subjects were studied. The hypertensives received their usual medication with the exception of spironolactone. All subjects underwent a standard saline infusion test (determination of plasma aldosterone before and after 2.0 liters of isotonic saline for 4 hours i.v.) and collected a 24 h urine sample for examination of urinary tetrahydroaldosterone and aldosterone-18-glucuronide. In hypokalaemic primary aldosteronism the saline infusion test showed a reasonable sensitivity (91%) and specificity (90%). However, the test failed to differentiate sufficiently between essential hypertension and normokalaemic primary aldosteronism (sensitivity 57%, specificity 90%). Similarly, urinary tetrahydroaldosterone had higher sensitivity in hypokalaemic than in normokalaemic primary aldosteronism (sensitivity 64% vs 36%, specificity 100%), whereas for aldosterone-18-glucuronide, no differences in hypo- and normokalaemic primary aldosteronism were found (sensitivity 45% and 43%, specificity 100%). These data show that the saline infusion test as an established test in classical hypokalaemic primary aldosteronism is not a reliable test in the normokalaemic variant of the disease. Due to its low accuracy, determination of urinary aldosterone metabolites did not prove useful in confirming either normo- or hypokalaemic patients. We conclude from our data that these tests should not be used as confirmatory testing in the normokalaemic variant of primary aldosteronism.

Urinary tetrahydroaldosterone as a screening method for primary aldosteronism: a comparative study

Background The major aldosterone metabolite 3α,5β tetrahydroaldosterone reflects up to 45% of the aldosterone secretion. Its 24-h urinary excretion is likely to provide an accurate index of the daily aldosterone production and to be an indicator for primary aldosteronism (PA). Methods In a prospective study, the validity of tetrahydroaldosterone as a screening test for PA was evaluated in comparison to serum potassium, plasma aldosterone, plasma renin activity, plasma aldosterone/renin activity ratio (PARR), as well as 24-h urinary aldosterone-18-glucuronide and free aldosterone. A total of 111 normotensive individuals, 412 PA patients and 1453 essential hypertensive patients, were studied. The effect of blood sampling technique on potassium level was also investigated. Results Tetrahydroaldosterone differentiated PA from essential hypertension with a sensitivity of 96% and a specificity of 95%. The sensitivity was 89% for plasma aldosterone, 87% for free aldosterone, 85% for PARR, 71% for aldosterone-18-glucuronide and 51% for renin activity. Specificities varied between 91% and 85%. The combined use of the parameters plasma aldosterone ≥9.0 ng/dL and PARR ≥25 resulted in a sensitivity of 82% and specificity of 95%. Forearm exercise proved to be a source of erroneous elevations of potassium sufficient to obscure the suspicion of PA. Conclusion The data suggest that tetrahydroaldosterone is the most reliable screening test for PA. Tetrahydroaldosterone determination in combination with aldosterone-18-glucuronide and free aldosterone increases diagnostic specificity for PA. Potassium, renin, plasma aldosterone, and basal PARR are inadequate screening procedures because they are subject to high rates of false-positive and false-negative results.

CYP11B2 polymorphisms and cardiovascular risk factors

CYP11B2 polymorphisms and cardiovascular risk factors

19-Noraldosterone in pregnancy-induced hypertension.

Pregnancy-induced hypertension (PIH) is a frequent cause of maternal and neonatal morbidity and mortality. 19-Noraldosterone, which was shown to be synthesized in the human adrenal gland, exhibits potent mineralocorticoid and hypertensive activity. To examine the role of mineralocorticoids in the pathophysiology of PIH, we studied urinary 19-noraldosterone, tetrahydroaldosterone, free cortisol, and cortisone concentrations and mineralocorticoid receptor levels in peripheral blood mononuclear leukocytes, from 17 women with PIH and 16 normal pregnant women as controls. Sequence analysis of the mineralocorticoid receptor gene in PIH patients was also done. The 24-h urinary excretion of 19-noraldosterone was significantly lower in PIH (120 +/- 38 pmol/day) than in controls (358 +/- 55 pmol/day) (P < 0.05). Urinary tetrahydroaldosterone was also decreased in PIH compared with controls. Ratios of urinary free cortisol to cortisone (a measure of 11beta-hydroxysteroid dehydrogenase 2 activity) did not differ significantly between groups. Mineralocorticoid receptor density was significantly (P < 0.05) decreased in the PIH group (133 +/- 15 binding sites/cell) compared with controls (255 +/- 21 binding sites/cell). No mutations were found in the coding region of the mineralocorticoid receptor gene in PIH. These results suggest that circulating aldosterone, 19-noraldosterone, and renal 11beta-hydroxysteroid dehydrogenase2 do not contribute to the pathogenesis of PIH. Regulatory factors that cause the down-regulation of the mineralocorticoid receptor in PIH should be clarified.

Urinary tetrahydro-aldosterone (thald) is yet the most reliable test for diagnosing primary aldosteronism (PA).

Urinary tetrahydro-aldosterone (thald) is yet the most reliable test for diagnosing primary aldosteronism (PA).

Alterations in Aldosterone Secretion and Metabolism in Low Renin Hypertension*

Low renin essential hypertensives (LRH) have normal plasma aldosterone levels which are inappropriately high in relation to their PRA. Posture is the major determinant for plasma aldosterone and PRA levels, but it is not known whether postural increments (delta) of plasma aldosterone and (delta) PRA are also abnormal in LRH. To evaluate this, LRH (n = 8), normal renin hypertensives (NRH; n = 9), normotensive controls (n = 18), and subjects with idiopathic hyperaldosteronism (IHA; n = 5) were studied in a metabolic unit on a controlled diet over 7 days. Overnight supine and 4-h upright PRA, plasma aldosterone, and 24-h urinary tetrahydroaldosterone (THA) and aldosterone secretion rates (ASR) were measured. The delta in plasma aldosterone after 4 h of upright posture was not different in the four groups. The ratio of delta plasma aldosterone/delta PRA, however, was elevated in both IHA and LRH compared to that in NRH and normals. THA excretion was also elevated in IHA and LRH, but LRH had a normal ASR. This resulted in a higher fractional THA excretion (THA/ASR) in LRH compared to the other three groups. These data further support enhanced adrenal angiotensin-II sensitivity in LRH. Aldosterone was preferentially metabolized to THA in LRH. Since THA has reduced biological activity, this may be a compensatory mechanism to reduce mineralocorticoid activity in LRH.

High-performance liquid chromatography in the radioimmunoassay of urinary tetrahydroaldosterone

High-performance liquid chromatography in the radioimmunoassay of urinary tetrahydroaldosterone

Improved gas chromatographic—mass fragmentographic assay for tetrahydroaldosterone and aldosterone in urine

A newly devised procedure for a simultaneous determination of urinary tetrahydroaldosterone and aldosterone is described. The procedure is based on deconjugation and acetalization, followed by extraction and derivatization of the urinary compounds to their trimethylsilyl ethers and subsequent gas chromatographic-mass fragmentographic detection. To evaluate the assay, aliquots of a urine sample of a healthy individual were analysed in multiplicate; a mean tetrahydroaidosterone concentration of 103 nmol/l and a within sample, within-day- and day-to-day coefficient of variation of 1.8, 3.2 and 3.4%, respectively, were found. Determination of aldosterone in the same sample yielded a mean concentration of 25.3 nmol/l and the following coefficients of variation: 2.8% (within-sample), 3.8% (within-day) and 4.3% (day-to-day). The urinary excretion of tetrahydroaldosterone and aldosterone in 24-h urine portions was determined in twenty healthy individuals, aged 23–77 years; for tetrahydroaldosterone and aldosterone, an excretion of 94 ± 66 nmol per 24 h and of 40 ± 22 nmol per 24 h was found, respectively, in accord with the literature. An example of the usefulness of the described assay is given by establishing the cause of severe salt-wasting in an infant; a highly elevated tetrahydroaldosterone and aldosterone excretion was demonstrated, proving that the child suffered from unresponsiveness to aldosterone (pseudohypoaldosteronism).

21-Deoxytetrahydroaldosterone excretion in primary hyperaldosteronism.

In earlier studies by our group it was shown that the urinary tetrahydroaldosterone excretion is a more reliable test for the diagnosis of primary aldosteronism than aldosterone-18-glucuronide ('urinary aldosterone'). However, in several patients with primary aldosteronism even the tetrahydroaldosterone values remained in the normal range. As the possible cause for this observation, the role of intestinal bacteria was considered which may transform tetrahydroaldosterone into 21-deoxytetrahydroaldosterone. Using a 21-deoxytetrahydroaldosterone radioimmunoassay, this hypothesis could be confirmed. The sums of the urinary 21-deoxytetrahydroaldosterone and tetrahydroaldosterone excretions revealed to be of better diagnostic value than the tetrahydroaldosterone values alone.

Neonatal diagnosis of orotic aciduria: An experience with one family

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