19-nordeoxycorticosterone and Hyperaldosteronism

Aldosterone-producing adenoma (APA) and idiopathic hyperplasia (IHA) are two main causes of primary hyperaldosteronism, which differ in the modes of treatment. Some of the prohormones, such as 18-hydroxycorticosterone, are elevated in adenomas. 19-Nor-deoxycorticosterone (19-nor-DOC), produced in the kidney, has been shown to be excreted in excess in patients with APA. Deoxycorticosterone is a known precursor of aldosterone and 19-nor-DOC. This study is designed to evaluate the levels of prohormones in adrenal venous effluent in eight patients, three with APA, of which two were confirmed by surgical pathology and four with IHA, and one patient with primary adrenal hyperplasia. 19-OH-DOC, a precursor of 19-nor-DOC, was found to be the main prohormone in adrenal venous effluent in patients with both APA and IHA. 19-Oic-deoxycorticosterone and 19-nor-DOC were also detected, but in smaller quantities. 19-OH-DOC appears to be the main prohormone in adrenal venous effluent for the biosynthesis of 19-nor-DOC.

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenal Glands; Adult; Aldosterone; Desoxycorticosterone; Female; Hormones; Humans; Hyperaldosteronism; Hyperplasia; Male; Middle Aged; Veins

19-Nor-deoxycorticosterone (19-nor-DOC) is a potent mineralocorticoid recently identified in human urine. The factors regulating 19-nor-DOC production are unknown; short term dietary sodium depletion or excess has little effect on 19-nor-DOC excretion in human subjects. This study sought to determine if more prolonged renin stimulation could increase 19-nor-DOC production. Six normal subjects were admitted to a metabolic unit. After a 5-day electrolyte balance period, hydrochlorothiazide (50 mg/day) was administered for 28 days. This treatment resulted in acute natriuresis, a more sustained hypokalemia, and secondary hyperaldosteronism lasting throughout the remainder of the study. Despite the sustained secondary hyperaldosteronism, however, urinary 19-nor-DOC extraction, measured by RIA, increased only slightly on day 3 and subsequently decreased to normal values throughout the remainder of the study (19-nor-DOC, 103 +/- 27 ng/day 0, 175 +/- 26 on day 3, 127 +/- 27 on day 28). The results of this study demonstrate only a minor and transient effect on diuretic-induced renin stimulation on 19-nor-DOC production. Therefore, the physiological regulation of 19-nor-DOC is largely independent of the renin-angiotensin system.

Topics: Adult; Chromatography, Thin Layer; Desoxycorticosterone; Female; Humans; Hydrochlorothiazide; Hyperaldosteronism; Male; Natriuresis; Potassium; Radioimmunoassay; Renin-Angiotensin System; Sodium; Time Factors

19-Nor-deoxycorticosterone (19-nor-DOC) is a naturally occurring, potent mineralocorticoid present in hypertensive animal models as well as man. To investigate 19-nor-DOC's regulation and possible pathogenesis in hypertension, urinary free (UF) 19-nor-DOC was measured in 14 hypertensives, correlated with other corticosteroids and systemic arterial blood pressure (BP), and compared to basal and ACTH-stimulated values in 8 normotensive subjects. Seven of the 14 hypertensives had low-renin hypertension, 2 had primary aldosteronism, 1 had an adrenal carcinoma, and another had acromegaly. These studies determined that: 1) although the mean UF 19-nor-DOC was not increased in hypertensives (588 +/- 180 vs. 428 +/- 122 ng/day), 2 low-renin hypertensives had quite elevated levels (2186 and 2018); 2) the UF 19-nor-DOC in hypertensives was correlated with BP but not with PRA, aldosterone secretion, plasma potassium, basal plasma cortisol, or 17-hydroxycorticosteroids; 3) likewise, in normotensives, UF 19-nor-DOC did not correlate with basal plasma cortisol, cortisol secretion, or 17-hydroxycorticosteroids excretion but did correlate after ACTH stimulation. Therefore, although 19-nor-DOC is activated by ACTH administration, it is not correlated with basal parameters of cortisol production, suggesting that factors other than ACTH regulate basal 19-nor-DOC secretion. Furthermore 19-nor-DOC is elevated in some hypertensive patients, and it is directly related to the elevation of mean systemic BP. This suggests that, although 19-nor-DOC could contribute to hypertensive disease in some individuals, it does not appear to be due to excess ACTH.

Topics: 17-Hydroxycorticosteroids; Acromegaly; Adrenal Cortex Neoplasms; Adrenocorticotropic Hormone; Adult; Aged; Blood Pressure; Desoxycorticosterone; Female; Humans; Hydrocortisone; Hyperaldosteronism; Hypertension; Male; Middle Aged; Pituitary Neoplasms; Renin

Nonaldosterone mineralocorticoids, such as deoxycorticosterone (DOC) and 18-hydroxy-DOC, have been reported to be elevated in some patients with primary aldosteronism (PA). Since DOC is a probable precursor of a more potent mineralocorticoid, 19-nor-deoxycorticosterone (19-nor-DOC), this study evaluated urinary free (UF) 19-nor-DOC excretion in 6 patients with PA and compared the results to those from 11 patients with low renin hypertension (LRH) and 7 normotensive subjects. PA was due to either an aldosterone-producing adenoma (APA; 4 patients) or bilateral adrenal hyperplasia (2 patients) diagnosed by adrenal venous catheterization or surgery. Compared to LRH subjects, patients with PA had a higher mean blood pressure (137 +/- 9 vs. 114 +/- 3 mm Hg), a lower plasma potassium level (3.1 +/- 0.2 vs. 3.9 +/- 0.1 meq/1) and greater renin suppression (0.3 +/- 0.1 vs. 0.6 +/- 0.1 ng angiotensin I/ml . h). UF 19-nor-DOC levels were elevated in PA subjects compared to those in normotensives (3,716 +/- 1,517 vs. 428 +/- 112 ng/day) but not compared to those in LRH patients (1,237 +/- 471). Two patients with APA had distinctly elevated UF 19-nor-DOC levels (11,137 and 7,744 ng/day), but another APA patient had the lowest value (305 ng/day). UF 19-nor-DOC positively correlated with the aldosterone secretion rate in PA (r = 0.75) but not LRH subjects. In conclusion, this study demonstrates that patients with PA may have elevated levels of UF 19-nor-DOC which are proportional to the aldosterone excess and could be a contributing factor to the hypertension, hypokalamia, and excess mineralocorticoid activity of this disease.

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenal Glands; Adult; Aged; Aldosterone; Desoxycorticosterone; Female; Humans; Hyperaldosteronism; Hyperplasia; Hypertension; Kinetics; Male; Middle Aged; Renin