Impairment of AVP regulation in 17alpha-hydroxylase deficiency, a unique form of adrenal insufficiency.

17alpha-hydroxylase deficiency (17alpha-OHDS) results in decreased production of cortisol and sex steroids and hypokalemia secondary to excess mineralocorticoids. It has long been known that glucocorticoid deficiency is associated with impaired urinary dilution and increased secretion of vasopressin (AVP). On the other hand, chronic hypokalemia is a well-established cause of nephrogenic diabetes insipidus. We evaluated the status of AVP secretion in a patient with 17alpha-OHDS and in 8 normokalaemic control subjects during hypertonic saline infusion (5% NaCl 0.06 ml.kg.min.120 min). The patient was evaluated on 3 separate occasions: pre-treatment (PT), and daily treatment with 0.375 mg (T1) and 0.5 mg (T2) dexamethasone. Blood was collected for AVP, corticosterone (B), plasma osmolality (pOsm) and electrolyte determination. In the control group plasma AVP levels increased from 0.8 +/- 0.1 to 4.1 +/- 0.6 pmol/l and pOsm increased from 282 +/- 2 to 302 +/- 11.5 mosmol/kg. In the patient, plasma AVP levels increased from 9.3 to 12.3; 4.5 to 6.2; and 2.5 to 6.2 pmol/l, and pOsm increased from 282 to 302, from 290 to 307, and from 291 to 311 mosmol/kg during the PT, T1 and T2 conditions, respectively. Serum potassium levels were low (2.6 mmol/l) during PT and reached normal values after treatment. There was a significant negative correlation between plasma AVP and serum potassium levels (r=-0.71; p<0.001). The results originally indicate that high plasma AVP levels may be found in 17alpha-OHDS, suggesting an effect of F deficiency per se. In addition, a concealed partial nephrogenic diabetes insipidus secondary to chronic hypokalemia cannot be excluded.