Tetrahydroaldosterone Excretion 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.

Cortisol Excess in Patients With Primary Aldosteronism Impacts Left Ventricular Hypertrophy.

Primary aldosteronism (PA) represents the most frequent form of endocrine hypertension. Hyperaldosteronism and hypercortisolism both induce excessive left ventricular hypertrophy (LVH) compared with matched essential hypertensives. In recent studies frequent cosecretion of cortisol and aldosterone has been reported in patients with PA. Our aim was to investigate the impact of cortisol cosecretion on LVH in patients with PA. We determined 24-hour excretion of mineralocorticoids and glucocorticoids by gas chromatography-mass spectrometry and assessed cardiac remodeling using echocardiography initially and 1 year after initiation of treatment of PA. We included 73 patients from the Munich center of the German Conn's registry: 45 with unilateral aldosterone-producing adenoma and 28 with bilateral adrenal hyperplasia. At the time of diagnosis, 85% of patients with PA showed LVH according to left ventricular mass index [(LVMI); median 62.4 g/m2.7]. LVMI correlated positively with total glucocorticoid excretion (r2 = 0.076, P = 0.018) as well as with tetrahydroaldosterone excretion (r2 = 0.070, P = 0.024). Adrenalectomy led to significantly reduced LVMI in aldosterone-producing adenoma (P < 0.001) whereas mineralocorticoid receptor antagonist therapy in bilateral adrenal patients with hyperplasia reduced LVMI to a lesser degree (P = 0.024). In multivariate analysis, the decrease in LVMI was positively correlated with total glucocorticoid excretion and systolic 24-hour blood pressure, but not with tetrahydroaldosterone excretion. Cortisol excess appears to have an additional impact on cardiac remodeling in patients with PA. Treatment of PA by either adrenalectomy or mineralocorticoid receptor antagonist improves LVMI. This effect was most pronounced in patients with high total glucocorticoid excretion.

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)

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.

High aldosterone-to-renin variants of CYP11B2 and pregnancy outcome

Increased aldosterone concentrations and volume expansion of normal pregnancies are hallmarks of normal pregnancies and blunted in pre-eclampsia. Accordingly, we hypothesized an active mineralocorticoid system to protect from pre-eclampsia. In pregnant women (normotensive n = 44; pre-eclamptic n = 48), blood pressure, urinary tetrahydro-aldosterone excretion and activating polymorphisms (SF-1 site and intron 2) of the aldosterone synthase gene (CYP11B2) were determined; 185 non-pregnant normotensive individuals served as control. Amino acid-changing polymorphisms of the DNA- and agonist-binding regions of the mineralocorticoid receptor were evaluated by RT-PCR, SSCP and sequencing. Urinary tetrahydro-aldosterone excretion was reduced in pre-eclampsia as compared to normal pregnancy (P < 0.05). It inversely correlated with blood pressure (r = 0.99, P < 0.04). Homozygosity for activating CYP11B2 polymorphisms was preferably present in normotensive as compared to pre-eclamptic pregnancies, identified (intron 2, P = 0.005; SF-1 site, P = 0.016). Two mutant haplotypes decreased the risk of developing pre-eclampsia (RR 0.16; CI 0.05-0.54; P < 0.001). In contrast, intron 2 wild type predisposed to pre-eclampsia (P < 0.0015). No functional mineralocorticoid receptor mutant has been observed. High aldosterone availability is associated with lower maternal blood pressure. In line with this observation, gain-of-function variants of the CYP11B2 reduce the risk of developing pre-eclampsia. Mutants of the mineralocorticoid receptor cannot explain the frequent syndrome of pre-eclampsia.

CYP11B2 polymorphisms and cardiovascular risk factors

CYP11B2 polymorphisms and cardiovascular risk factors

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.

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).

Urinary excretion of kallikrein before and after operation for aldosterone-producing adenoma.

Urinary kallikrein excretion (UKal), determined by the esterase method, was measured in 10 normotensive volunteers, 10 patients with essential hypertension and in 7 patients with primary aldosteronism before and after operative removal of the adenoma. UKal values were low in 5 of the patients with essential hypertension. Preoperative UKal values in the patients with aldosteronism did not differ significantly from those of the normal subjects, but decreased in all after operation in parallel with changes in urinary excretion of tetrahydroaldosterone and plasma aldosterone concentration. The study supports the assumption of an association between the renal kallikrein-kinin system and the mineralocorticoid state in man.

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.

The effects of hydrochlorothiazide on the renin-aldosterone system

This study prospectively evaluates the determinants and time course of diuretic-induced secondary hyperaldosteronism. Initial metabolic balance studies (days 5–7) and subsequent out-patient studies (days 8–28) were undertaken in 6 healthy subjects receiving hydrochlorothiazide 50 mg/day. Upon initiation of therapy, a discordance was observed between the natriuresis (maximal on day 1), the plasma renin activity (PRA) (maximal on day 3), and aldosterone secretion (maximal on day 7). The PRA increment correlated best with the urinary sodium deficit and the aldosterone increment correlated best with both PRA and urinary sodium deficit together. The secondary hyperaldosteronism persisted throughout the study, as determined by the aldosterone secretion rate, but the tetrahydroaldosterone excretion and the plasma aldosterone became normal within 3 wk of diuretic therapy. Hypokalemia also persisted throughout the study and was probably related to the secondary hyperaldosteronism since the urinary potassium deficit correlated with the aldosterone secretion but not the sodium excretion. In conclusion, (1) the urinary sodium deficit is the major determinant of diuretic-induced secondary hyperaldosteronism, (2) secondary hyperaldosteronism is the most important factor maintaining diuretic-induced hypokalemia, and (3) secondary hyperaldosteronism may be overlooked if only tetrahydroaldosterone excretion or plasma aldosterone levels are measured during diuretic therapy.

Altered fractional tetrahydroaldosterone excretion during pharmacological blockade and activation of the renin-aldosterone system.

Tetrahydroaldosterone (THA) is the principal metabolite and generally a good index of aldosterone secretion. This study undertakes the evaluation of the aldosterone secretion rate (ASR) and excretion of THA during pharmacological blockade and activation of the renin-aldosterone system. THA was measured by a simplified RIA and compared to ASR over a period of 28 days in 18 normotensive volunteers receiving either 1) a diuretic [hydrochlorthiazide (HCTZ), 50 mg/day], 2) an angiotensin-converting enzyme inhibitor (MK-421, 10 mg/day), or 3) combined therapy [HCTZ (50 md/day) plus MK-421 (10 mg/day)] in a metabolic unit on a controlled diet. Results of this study at 28 days indicate that 1) HCTZ, while producing secondary hyperaldosteronism, lowered the fractional THA excretion (defined as THA/ASR) (from 0.51 to 0.33; P less than 0.05); 2) MK-421 produced hypoaldosteronism and a slight increase in the THA/ASR (from 0.43 to 0.53; 0.05 less than P less than 0.01); 3) combined HCTZ and MK-421 resulted in a normalization of both aldosterone secretion and THA/ASR (from 0.51 to 0.50). In conclusion, HCTZ decreases the THA/ASR whereas MK-421 tends to increase it. Combined administration of HCTZ and MK-421 restores the THS/ASR to normal. Therefore, the determination of THA excretion can be an inaccurate index of aldosterone secretion when measured during either pharmacological blockade or activation of the renin-aldosterone system.

Temporal enhancement of renin-aldosterone blockade by enalapril, an angiotensin-converting enzyme inhibitor.

Interruption of the renin-aldosterone system with angiotensin-converting enzyme inhibitors (CEI) should result in a low aldosterone secretion, but most investigators have measured aldosterone production only indirectly by plasma aldosterone (PA) levels or urinary metabolites. We evaluated the effects of CEI of the aldosterone secretion rate (ASR) and compared them with PA, urinary tetrahydroaldosterone (THA), plasma renin activity (PRA), and electrolyte balance in six normotensive subjects in a metabolic unit during a control period (5 days) and during administration of 10 mg/day enalapril for 28 days. Our results demonstrated that (1) the ASR did not decline until after 1 wk of CEI therapy and this was reflected by a corresponding decline in the urine potassium:sodium ratio, (2) upright PA levels at day 1 declined, but supine PA levels were unchanged, (3) THA excretion remained essentially unchanged and the THA:ASR ratio rose progressively during therapy, (4) PRA rose and was maximal on day 3, but subsequently declined. In conclusion, enalapril-induced hypoaldosteronism required several days to become demonstrable and this was not accurately assessed by PA or THA--possibly due, in part, to altered aldosterone metabolism. The simultaneous decline in both PRA and ASR could be due to a decrease in renin substrate. Caution is therefore warranted when assessing aldosterone secretion indirectly by either PA levels or urinary metabolites during CEI therapy.

Urinary free 18-hydroxycorticosterone, plasma aldosterone, and urinary aldosterone metabolites in normal pregnancy

The final steps in aldosterone biosynthesis are unclear. Undecided is whether 18-hydroxycorticosterone is a precursor of aldosterone or an end product. 18-Hydroxycorticosterone is secreted in close relationship to aldosterone. To get adequate information on the status of aldosterone in pregnancy, determination of more than one parameter of aldosterone seems to be necessary. Urinary excretion of free 18-hydroxycorticosterone, tetrahydroaldosterone, aldosterone-18-glucuronide, free aldosterone, and the plasma concentration of aldosterone were measured by radioimmunoassay in 16 primigravid women in the last trimester of normal pregnancy and in 13 healthy nonpregnant women. All steroids measured were significantly increased in pregnancy. The ratios of aldosterone-18-glucuronide to tetrahydroaldosterone in the two groups were not significantly different, so that significant changes in renal or hepatic aldosterone metabolism could not be demonstrated in pregnancy. When pregnant women with ankle edema (n = 7) were compared to pregnant women without edema (n = 9), no differences in steroid patterns could be found. The increased excretion of 18-hydroxycorticosterone in pregnancy confirms the state of hyperaldosteronism in normal pregnancy which is associated with an increase in biologically active, free aldosterone. Dissociation in the excretion of the two aldosterone metabolites and free aldosterone was found in three pregnant women, in whom excretion of aldosterone-18-glucuronide was increased but excretion of tetrahydroaldosterone and free aldosterone was in the normal nonpregnant range.

Analysis of steroids in urine for differentiation of pseudohypoaldosteronism and aldosterone biosynthetic defect.

The salt-losing syndromes in the neonatal period and early infancy due to adrenal disease can be differentiated by the pattern of excretion of steroids in urine. The presence or absence of metabolites of cortisol, aldosterone, and corticosterone as well as certain precursors can be established in a single analysis of steroids in urine by using gas chromatography with open tubular capillary columns. The profiles of steroid excretion in the urine of 8 infants with renal tubular insensitivity to aldosterone were compared with those in 5 infants with isolated aldosterone biosynthetic defects. The excretion in urine of 18 hydroxytetrahydro-compound A was elevated in all 13 children, but relative to the excretion of tetrahydroaldosterone, a high ratio was found for the biosynthetic defect and clearly distinguished the 2 conditions. Age-related changes in steroid metabolism are described. The diagnosis in each case was supported by clinical investigation together with determinations of PRA and aldosterone concentrations.

Determination of urinary tetrahydroaldosterone glucosiduronic acid by radioimmunoassay

A procedure is described for determining tetrahydroaldosterone 3-glucosiduronic acid in unprocessed human urine by radioimmunoassay. The procedure is simple, accurate and requires relatively little time. Data on cross reactivity, on within-assay and betweeen-assay variability, and on reliability are given. Values for urinary excretion of tetrahydroaldosterone, aldosterone and sodium are given for a group of 72 normal individuals (35 M; 37 F) who were on ad libitum salt intake. The average excretion of tetrahydroaldosterone is 5.3 times as great as that of aldosterone and the range of deviation (in percent) from the mean value is the same for tetrahydroaldosterone as for aldosterone.

Dissociation in the excretion of different aldosterone metabolites and unmetabolized ('free') aldosterone in hypertension.

1. The determination of aldosterone-18-glucuronide (pH 1-labile aldosterone) was complemented by concomitant measurements of free urinary aldosterone and tetrahydroaldosterone in 307 patients, most of whom were hypertensive. In 38 cases (12.3%) the normal, aldosterone-18-glucuronide concentration was clinically misleading, but increased free aldosterone and/or tetrahydroaldosterone values suggested the presence of hyperaldosteronism, which in many of these cases was confirmed by elevated excretion of the possible major aldosterone precursor 18-hydroxycorticosterone (18-OH-B). 2. Of 224 patients with essential hypertension and normal or low plasma renin activity 18 had an elevated free aldosterone and/or tetrahydroaldosterone excretion without increased aldosterone-18-glucuronide. These cases may represent early or pre-symptomatic forms of primary hyperaldosteronism. In other cases, particularly when tetrahydroaldosterone was increased alone, abnormalities of aldosterone metabolism were suspected. 3. In two out of 15 patients with primary hyperaldosteronism, aldosterone-18-glucuronide values were frequently found to be normal, although elevations were noted in other variables. However, no relation to the morphological abnormality (adenoma versus hyperplasia) was seen.

Treatment of Cushing's Syndrome with Trilostane (WIN 24,540), an Inhibitor of Adrenal Steroid Biosynthesis*

Seven patients with Cushing's syndrome were treated with trilostane (WIN 24,540) 4 alpha,5-epoxy-17 beta-hydroxy-3-oxo-5 alpha-androstane-2 alpha-carbonitrile), an inhibitor of adrenal steroid biosynthesis. Trilostane treatment reduced steroid biosynthesis and it also improved biochemical manifestations of the disease in all of the patients treated. The average cortisol secretory rate decreased significantly with treatment, from 47.1 to 23.4 mg/24 h (P less than 0.005), and urinary 17-hydroxycorticosteroids decreased from 15.7 to 8.7 mg/24 h (P less than 0.01). Urinary free cortisol excretion decreased from 277 to 88 microgram/24 h (P less than 0.01), and 0800 h plasma cortisol levels declined from 25.0 to 12.0 microgram/dl (P less than 0.05). Conversely, dehydroepiandrosterone sulfate excretion in urine increased from 1.3 to 5.8 mg/24 h (P less than 0.0025) and in plasma increased from 162 mg/24 h (P less than 0.025). Plasma and urinary free dehydroepiandrosterone increased 2-fold. Urinary 17-ketosteroid excretion increased from 18 to 43 mg/24 h (P less than 0.001). A significant reduction in urinary excretion of tetrahydroaldosterone, tetrahydrodeoxycorticosterone, and 18-hydroxytetrahydrodeoxycorticosterone was observed with treatment. Inhibition of steroid biosynthesis was accompanied by a 2-fold increase in PRA and no change in serum cholesterol levels. Mean arterial blood pressure decreased with treatment from 109 to 97 mm Hg (P less than 0.005), and fasting blood sugar decreased from 117 to 98 mg/dl (P less than 0.005), accompanied by rise in plasma potassium levels from 3.8 to 4.3 milliequivalents/liter (P less than 0.025). Two patients on long term therapy also showed an improvement in clinical features of their disease. There were no significant treatment-related carcinoma, simultaneously producing both an excessive amount of cortisol and ACTH, is described. It is concluded that trilostane is an effective inhibitor of 3 beta-hydroxysteroid dehydrogenase enzyme system in human adrenal gland; it inhibits biosynthesis of cortisol and it is useful in the treatment of Cushing's syndrome.

Aldosterone metabolism after prolonged ACTH administration in juvenile hypertension

The effect of a 5-day continuous ACTH infusion (Acthar, 40 U/24h) on aldosterone metabolism was evaluated in 3 hypertensive children with hyperaldosteronism, 2 children with essential hypertension, and 1 normotensive control. Plasma aldosterone concentration(PA) and urinary excretion of aldosterone pH1 conjugate(pH1A), tetrahydroaldosterone(THA) and free aldosterone (FA) were measured by radioimmunoassay. In the patients with hyperaldosteronism, PA rose 3-fold and the 3 urinary metabolites showed a sustained 5-fold increase throughout the ACTH test. In the other children, PA and urinary aldosterone. metabolites rose 2-4 fold on the 1st day of ACTH administration, but decreased on the 4th and 5th day. pH1A fell more rapidly than either THA or FA. Consequently, the THA/pH1A ratio rose from 3.0 to 8.6 during the 5-day ACTH test. Conclusions: 1)prolonged ACTH administration induces a shift in the excretory pattern of the aldosterone metabolites leading to increased excretion of THA and FA; 2)pH1A alone is not an adequate index of aldosterone secretion in prolonged ACTH administration; 3) in hyperaldosteronism, ACTH produces an unusual sustained increase of all aldosterone metabolites.

Radioimmunological determination of urinary tetrahydroaldosterone

A method is presented for radioimmunological determination of 3alpha, 5beta-tetrahydroaldosterone. It is based upon the reactivity of this steroid with an antiserum induced by the 3-carboxymethyloxime of 18, 21-aldosterone diacetate conjugated with bovine serum albumin. One hundred microliters of urine enzymatically hydrolyzed with an helix pomatia preparation, containing tritiated tetrahydroaldosterone for the yield calculation, were extracted with dichloromethane and chromatographed on a small celite column. The yield after extraction and chromatography was 64 +/- 17%. The radioimmunological determination was carried out in a conventional manner. The method is specific, sensitive (10 pg/tube), exact, reproducible, very simple and extremely rapid. The results showed good agreement with values given by a colorimetric method (p less than 0.001). The median value measured in 45 healthy adult subjects under standard sodium diet was 53.3 microgram/24h (95 % of the population within a 16.6 to 131.1 microgram/24h range). In 78 cases of adrenocortical insufficiency, 60 cases of obesity and 28 cases of hypokalemia, the median values (and the ranges : microgram/24h) were respectively 7.7 (1.0 - 51.0), 80.9 (17.0 - 503.0) and 64.3 (8.0 - 181.0). In 330 hypertensive patients the excretion of tetrahydroaldosterone exceeded the normal range in 115 cases (35%) with a median of 199.7 microgram/24h (131 to 620 microgram/24h).