T. J. Benraad

Hypotensive effects of ovine and human corticotrophin-releasing factors in man

SummaryThe haemodynamic effects of i.v. bolus injections of 100 and 200 µg ovine CRF and human CRF in man have been compared. Neither ovine CRF 100 µg nor human CRF 100 µg caused a significant change in blood pressure, although the pulse rate was increased in all the subjects tested. The mean maximum increase in pulse rate after human CRF was almost twice that after ovine CRF (21 vs 12 beats·min−1;p<0.05). After 200 µg ovine CRF in all subjects the diastolic blood pressure declined gradually from 77 mm Hg to a nadir of 67 mm Hg at 22 min (p<0.002). After 200 µg human CRF diastolic blood pressure fell from 78 mm Hg to a nadir of 61 mm Hg at 6 min (p<0.002); the fall after human CRF was significantly greater than after ovine CRF (p<0.05). After 200 µg ovine CRF there was a slight increase in pulse rate lasting for 6 min, and after 200 µg human CRF there was a marked (reflex) tachycardia for 30 min. Only after the highest dose of human CRF did a slight increase in systolic blood pressure occur. The haemodynamic effects of both doses of human CRF were accompanied by significant increases in plasma noradrenaline concentrations, which were significantly greater after the higher dose.

Differential effects of ovine and human corticotrophin-releasing factor in human subjects.

Ten healthy subjects received 200 μg of human CRF (hCRF) and 200 μg of ovine CRF (oCRF) as an intravenous bolus injection on two different occasions. After hCRF plasma ACTH levels rose significantly (P< 0.0005, by Friedmans nonparametric analysis of variance) from a basal value of 35 ± 3 pg/ml (mean ± SEM) to a peak value of 80 ± 7 pg/ml 30 min after hCRF administration. This ACTH response was followed by a rise in plasma cortisol levels (P< 0.0005, by Friedmans test) from a baseline value of 0.32 ± 0.03 /μmol/l to a peak value of 0.56 ± 0.02 /μmol/l 60 min after hCRF. Ovine CRF elicited similar rises in the plasma ACTH and cortisol levels. However, as derived from the faster rate of decline of ACTH and cortisol after hCRF than after oCRF, human CRF had a significantly shorter duration of action than ovine CRF in humans. Human CRF not only stimulated ACTH release by the human pituitary gland but also prolactin release. After hCRF administration prolactin levels rose significantly (P< 0.005, by Friedmans test) from a basal value of 179 ± 18 mU/l to a peak value of 288 ± 34 mU/l at 10 min.

ACTH and cortisol responses to ovine corticotrophin-releasing factor in patients with primary and secondary adrenal failure

The ACTH and cortisol responses to an intravenous bolus injection of 100 μg ovine CRF were studied in 19 patients with adrenal failure. In all eight patients with primary adrenal failure, plasma ACTH levels increased from a mean basal level of 1494·431 (SEM) pg/ml to a peak value of 2601±220 pg/ml at 10 min. In comparison with healthy subjects absolute ACTH increments after ovine CRF were significantly augmented in the patients with Addisons disease (P* > 0.001), and the absolute ACTH responses after ovine CRF were positively correlated with the basal plasma ACTH levels. The 11 patients with secondary adrenal insufficiency could be subdivided into two groups: (A) those having little or no ACTH and cortisol response to ovine CRF (five patients) and (B) those having prolonged and pronounced ACTH responses with a biphasic pattern and a delayed second peak (six patients), followed in all patients by a marked cortisol increase. These data demonstrate that the CRF‐test can discriminate between hypothalamic and pituitary causes of secondary adrenal failure.

DEXAMETHASONE-RESPONSIVE HYPERTENSION IN YOUNG WOMEN WITH SUPPRESSED RENIN AND ALDOSTERONE

Pronounced hypoaldosteronism was found in three young women with hypertension and symptoms of mineralocorticoid overproduction--i.e., hyporeninaemia, hypokalaemia, and a fall in blood-pressure after diuretic therapy. Plasma 11-deoxycorticosterone and 18-hydroxy-11-dooxycorticosterone concentrations were normal Treatment with dexamethasone induced a return to normal of blood-pressure and plasma-potassium and an increase in plasma-renin activity and urinary aldosterone excretion. The data suggest that hypertension in these patients is maintained by overproduction of an unknown adrenocorticotropindependent mineralocortocoid.