Aldosterone synthesis in salt-wasting congenital adrenal hyperplasia with complete absence of adrenal 21-hydroxylase

Phyllis W. Speiser, Levon Agdere, Hajime Ueshiba, Perrin C. White, Maria I. New

Research output: Contribution to journalArticle

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Abstract

Background. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is a disorder of cortisol and aldosterone biosynthesis that results from mutations in the CYP21 gene encoding the adrenal 21-hydroxylase p-450c21. It can cause severe salt wasting in newborns that requires long-term treatment with glucocorticoids and mineralocorticoids. We describe a spontaneous partial recovery from this disorder in a 19-year-old woman who had discontinued treatment. Methods. We measured plasma and urinary levels of adrenal hormones, plasma renin activity, and sodium balance longitudinally in the patient and four other patients in whom adrenal hyperplasia had been diagnosed in infancy and in whom DNA analysis had predicted a complete absence of functional P-450c21. The ratio of plasma renin activity to urinary aldosterone was used as a measure of the response of the adrenal zona glomerulosa. Two patients underwent intravenous infusion of [3H]progesterone for the measurement of extraadrenal production of 21-hydroxylated precursors of aldosterone. Results. The patient who had discontinued her medication excreted a normal amount of aldosterone (20.0 nmol per square meter of body-surface area per day) while following a diet low in sodium. Her ratio of plasma renin activity to urinary aldosterone-18-glucuronide excretion was 1.7 after three days of sodium restriction, as compared with a ratio of 4.7 at the age of nine years (normal range, 0.03 to 0.1). The percentage of extraadrenal conversion of progesterone to deoxycorticosterone was low. The four other patients had variable responses to sodium restriction after the neonatal period (range for plasma renin activity:urinary aldosterone-18-glucuronide, 1.9 to 19.4). Conclusions. Although patients with salt-wasting 21-hydroxylase deficiency have functionally equivalent mutations in their CYP21 genes, they may vary from one another and over time in their ability to produce mineralo-corticoids. This variation may be attributable to another adrenal enzyme with 21-hydroxylase activity.

Original languageEnglish (US)
Pages (from-to)145-149
Number of pages5
JournalNew England Journal of Medicine
Volume324
Issue number3
StatePublished - Jan 17 1991

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Steroid 21-Hydroxylase
Congenital Adrenal Hyperplasia
Aldosterone
Salts
Renin
Zona Glomerulosa
Sodium
Progesterone
Sodium-Restricted Diet
Desoxycorticosterone
Mineralocorticoids
Mutation
Body Surface Area
Intravenous Infusions
Glucocorticoids
Genes
Hyperplasia
Hydrocortisone
Adrenal Cortex Hormones
Reference Values

ASJC Scopus subject areas

  • Medicine(all)

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Aldosterone synthesis in salt-wasting congenital adrenal hyperplasia with complete absence of adrenal 21-hydroxylase. / Speiser, Phyllis W.; Agdere, Levon; Ueshiba, Hajime; White, Perrin C.; New, Maria I.

In: New England Journal of Medicine, Vol. 324, No. 3, 17.01.1991, p. 145-149.

Research output: Contribution to journalArticle

Speiser, Phyllis W. ; Agdere, Levon ; Ueshiba, Hajime ; White, Perrin C. ; New, Maria I. / Aldosterone synthesis in salt-wasting congenital adrenal hyperplasia with complete absence of adrenal 21-hydroxylase. In: New England Journal of Medicine. 1991 ; Vol. 324, No. 3. pp. 145-149.
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AU - White, Perrin C.

AU - New, Maria I.

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AB - Background. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is a disorder of cortisol and aldosterone biosynthesis that results from mutations in the CYP21 gene encoding the adrenal 21-hydroxylase p-450c21. It can cause severe salt wasting in newborns that requires long-term treatment with glucocorticoids and mineralocorticoids. We describe a spontaneous partial recovery from this disorder in a 19-year-old woman who had discontinued treatment. Methods. We measured plasma and urinary levels of adrenal hormones, plasma renin activity, and sodium balance longitudinally in the patient and four other patients in whom adrenal hyperplasia had been diagnosed in infancy and in whom DNA analysis had predicted a complete absence of functional P-450c21. The ratio of plasma renin activity to urinary aldosterone was used as a measure of the response of the adrenal zona glomerulosa. Two patients underwent intravenous infusion of [3H]progesterone for the measurement of extraadrenal production of 21-hydroxylated precursors of aldosterone. Results. The patient who had discontinued her medication excreted a normal amount of aldosterone (20.0 nmol per square meter of body-surface area per day) while following a diet low in sodium. Her ratio of plasma renin activity to urinary aldosterone-18-glucuronide excretion was 1.7 after three days of sodium restriction, as compared with a ratio of 4.7 at the age of nine years (normal range, 0.03 to 0.1). The percentage of extraadrenal conversion of progesterone to deoxycorticosterone was low. The four other patients had variable responses to sodium restriction after the neonatal period (range for plasma renin activity:urinary aldosterone-18-glucuronide, 1.9 to 19.4). Conclusions. Although patients with salt-wasting 21-hydroxylase deficiency have functionally equivalent mutations in their CYP21 genes, they may vary from one another and over time in their ability to produce mineralo-corticoids. This variation may be attributable to another adrenal enzyme with 21-hydroxylase activity.

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