Combined 17 alpha- and 18-hydroxylase deficiency associated with complete male pseudohermaphroditism and hypoaldosteronism

Abstract

A 15-year-old phenotypic female with XY genotype presented with male pseudohermaphroditism, gynecomastia, hypokalemic alkalosis, and hypertension. Being raised as a girl, the patient failed to menstruate and developed no sexual hair. At laparatomy no Müllerian structures were found but testes were removed which showed histologically atrophy of seminiferous tubules and abundant Leydig cells. Deoxycorticosterone (2.0 mg/24 h) and corticosterone (117 mg/24 h) secretion rates were extremely elevated, whereas those of aldosterone (17 micrograms/24 h), deoxycortisol (22 micrograms/24 h), and cortisol (23 micrograms/24 h) were almost unmeasurable. The excretion rates of 18-OH-deoxycorticosterone (less than 0.25 microgram/24 h) and 18-OH-corticosterone (3.0 microgram/24 h) were subnormal in spite of high plasma ACTH levels (200 pg/ml), and deoxycorticosterone (32.2 micrograms/24 h) and corticosterone (269 micrograms/24 h) excess. Gonadotropins were elevated. Deficient 17 alpha-hydroxylation was suspected because of: 1) low levels of 17 alpha-OH-progesterone; 2) diminished excretion rates of both 17 alpha-OH-progesterone and pregnanetriol; and 3) reduced concentrations of dehydroepiandrosterone, androstenedione, and testosterone in testicular tissue. We conclude that this male pseudohermaphrodite with complete female phenotype had 17 alpha-hydroxylase deficiency. The enzymatic defect was linked with an associated 18-hydroxylase deficiency.