17 alpha-Hydroxylase deficiency. A combination of hydroxylation defect and reversible blockade in aldosterone biosynthesis.
We have studied the hormonal secretion and excretion patterns in a patient with the XX type of 17 alpha-hydroxylase deficiency. In the untreated state, the patient's urine contained only those steroids which do not require 17-hydroxylation in their biosynthesis. Aldosterone was not produced in the patient and the metabolic product of its immediate precursor, 18-hydroxy-11-dehydro-tetrahydrocorticosterone, was excreted in markedly elevated amounts. This apparent complete block in 18 oxidation was reversible upon long-term ACTH suppression within 27 days. Direct in vitro incubation of the patient's adrenal gland removed at operation demonstrated, 1) the complete lack of 17 alpha-hydroxylase activity, 2) the functional block in the ability to oxidize the hydroxyl group at the 18 methyl side chain. The addition of physiological concentrations of angiotensin to the incubation medium further showed, 3) angiotensin mildly stimulated the entire aldosterone biosynthetic pathway, 4) angiotensin directly stimulated the conversion of 18-hydroxycorticosterone to aldosterone. We propose that in this patient, 17-hydroxylase deficiency produced a decreased plasma concentration of cortisol, followed by stimulation of deoxycorticosterone production by ACTH. The resultant increase in extracellular fluid volume suppressed plasma renin activity. This resulted in a low plasma concentration of angiotensin II which directly suppressed oxidation of 18-hydroxycorticosterone to aldosterone. This defect has been called corticosterone methyl oxidase defect type 2.
D015069:18-Hydroxycorticosterone / Q000378:metabolism; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000378:metabolism; D000311:Adrenal Glands / Q000378:metabolism; D000308:Adrenocortical Hyperfunction / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage; D000450:Aldosterone / Q000096:biosynthesis*; D002845:Chromatography; D003907:Dexamethasone / Q000627:therapeutic use; D004573:Electrolytes / Q000097:blood; D005260:Female; D006801:Humans; D006899:Mixed Function Oxygenases / Q000172:deficiency*; D011241:Prednisone / Q000627:therapeutic use; D012083:Renin / Q000097:blood; D012964:Sodium / Q000008:administration & dosage
D000305:Adrenal Cortex Hormones; D004573:Electrolytes; D000450:Aldosterone; D015069:18-Hydroxycorticosterone; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D012964:Sodium; D006899:Mixed Function Oxygenases; D012083:Renin; D011241:Prednisone