Figure 1.
Flow chart indicating the different phases of the study to week four as recommended by the TREND statement [14].
Analysis performed at week four as all six patients had insulin resistance and blood pressure measurements suitable for analysis.
Figure 2.
Study Design showing investigations and intervention performed on six patients from baseline to four weeks.
One subject was withdrawn after end of second week. 1variables measured at baseline and end of study. OGTT: Oral Glucose Tolerance Test - insulin & glucose at 0, 15, 30, 60, 90, 120 min, F: cortisol, ACTH: Adrenocorticotropic Hormone, U & E: urea, electrolytes and creatinine, LFT: Liver Function Tests, FBC: Full Blood Count, TFT: Thyroid Function Tests.
Table 1.
Demographic data – Subject Baseline Characteristics.
Figure 3.
a: Graph showing mean ±SEM 0900 h serum cortisol and ACTH levels at baseline and 4 weeks.
Activation of the HPA axis, that is a rise in serum cortisol and ACTH, is already evident one week after starting mifepristone. b: Graph showing mean ±SEM 0900 h and 2300 h salivary cortisol levels at baseline and 4 weeks. Circadian rhythm of cortisol is maintained evidenced by high levels at 0900 h and low levels at 2300 h, but amplified by the use of mifepristone 200 mg twice per day.
Figure 4.
Graphs showing the changes in insulin AUC pre (red circle) and post (black square) mifepristone.
The upper white area represents insulin AUC levels associated with increased risk for cardiovascular (CV) events. The grey shaded area represents the insulin AUC upper and lower 95% reference range (not associated with cardiovascular events). Mean: 26940 pmol/l.min; 2SD: 63420 pmol/l.min. Subjects 2 and 5 show a clinically significant improvement in their insulin AUC post mifepristone (dotted arrow). Subjects 1 and 6 both show a reduction in insulin AUC from the upper to the lower 95% reference range (solid arrow). Patient 4 remains at CV risk post mifepristone, indicating no clinical benefit. The insulin AUC is plotted on the y axis as a logarithmic scale to base 4.
Table 2.
Baseline and 4 week insulin sensitivity and glucose tolerance data after the use of mifepristone in 6 patients.