Possible Hyperaldosteronism and Discrepancy in Enzyme Activity Deficiency in Adrenal and Gonadal Glands in Japanese Patients with 17 .ALPHA.-Hydroxylase Deficiency.

Abstract

We reviewed the pathophysiology of our previously reported female patient who had glucocorticoid-responsive hyperaldosteronism and was treated successfully with daily dose of dexamethasone (Dex) for 21 years. In this present study, the possibility that the patient may have 17 alpha-hydroxylase deficiency (17-OH-D) mainly in the adrenal could not be ruled out. We therefore reviewed 31 Japanese patients diagnosed as having 17-OH-D with suppressed plasma renin activity reported in Japan. Among these patients, 9 were found to have a high plasma aldosterone (Ald) concentration (PAC) (group I). Twenty-one patients had either normal or low-normal PAC and the remaining patient had low urine Ald (group II). The slight cross-reactivity of the anti-Ald-antibodies used with 17-deoxy-steroids such as progesterone, 11-deoxycorticosterone and corticosterone which were increased in both groups did not explain the increased PAC in group I. In the patients in group I and group II with high-normal basal PAC, PAC further increased after ACTH and was suppressed by Dex. PAC in 2 group I patients, however, did not respond to angiotensin-II or angiotensin-III infusion. PAC in patients in group II with low or low-normal basal PAC responded equivocally to ACTH and Dex. The basal plasma cortisol in group I was lower than in group II, and plasma cortisol level after ACTH in group I appeared to remain at a lower level than that in group II patients. Among the study subjects, 28 showed a negative correlation between basal PAC and plasma cortisol. A possible discrepancy in the deficiency of 17 alpha-hydroxylase activity in adrenal and gonadal glands was also suggested in three 17-OH-D patients. The pathophysiology of Ald secretion and discrepancy in the deficiency of the enzyme activities in both glands in 17-OH-D patients was discussed.

P450c17 Deficiency Caused by Compound Heterozygosity for Two Novel Mutations Presenting as Hypotension in Early Infancy

“…Classically, suppressed renin is associated with low aldosterone in CYP17A1 deficiency. However, aldosterone levels have been detectable or even elevated in several other cases of CYP17A1 deficiency [2,35]. Cross-reactivity of other compounds in the aldosterone radioimmunoassay has been one proposed mechanism for this unexpected finding [5,35].…”

“…However, aldosterone levels have been detectable or even elevated in several other cases of CYP17A1 deficiency [2,35]. Cross-reactivity of other compounds in the aldosterone radioimmunoassay has been one proposed mechanism for this unexpected finding [5,35]. However, Yamakita et al [35] repeated the measurement of aldosterone in 2 of their subjects using two different assays (albeit both radioimmunoassays) with similar results.…”

“…Cross-reactivity of other compounds in the aldosterone radioimmunoassay has been one proposed mechanism for this unexpected finding [5,35]. However, Yamakita et al [35] repeated the measurement of aldosterone in 2 of their subjects using two different assays (albeit both radioimmunoassays) with similar results. In addition, they found a negative correlation between residual P450c17 activity (as indicated by cortisol level) and aldosterone level, suggesting that the severity of the cortisol deficiency was associated with enhanced aldosterone production.…”

Testicular Adrenal-Like Tissue in a Patient with 17α-Hydroxylase Deficiency

“…The pathogenic mecha nism of the high aldosterone levels in these patients is unknown. Interestingly Yamakita et al [21] have pointed out that Japanese cases with hyperaldosteronism showed a lower 17a-hydroxylase activity since these patients showed lower levels of serum cortisol and DHEA and a lower response of cortisol to ACTH stimulation. The authors have speculated that the lower the 1701-hydroxy lase activity the greater the increase of corticosterone methyloxidase II activity in the zona fasciculata.…”

A Case of 17.ALPHA.-Hydroxylase Deficiency with Retained Menstruation.

“…indicated that the normal or increased aldosterone levels might be derived from cross-reaction in the aldosterone radioimmunoassay with other increased steroids such as DOC or corticosterone [2], such cross-reactions are generally considered to be minimal in the assay employed [20]. It has been suggested that continuously increased ACTH might stimulate aldosterone synthesis through the enhancement of P450 corticosterone methyloxidase activity which has been observed especially in cases of a marked decrease in serum cortisol and an associated increase in plasma ACTH [21]. It is noteworthy that the plasma aldosterone level in the present case decreased transiently below normal after dexamethasone administration along with the decrease in the plasma ACTH level and returned to normal subsequent to the increase in PRA.…”