The biggest danger of taking too little corticosteroid to replace what is lost is a condition called a "syndrome of secondary mineralocorticoid excess." This occurs because the pituitary gland reacts to the lack of cortisol by producing a hormone called ACTH (this is called "negative feedback"). ACTH increases the production of mineralocorticoids (like aldosterone), hormones that increase blood pressure, lower potassium and cause edema in the limbs.
Cortisol has many functions, including energy production, control of inflammatory response (e.g., preventing arthritis), and preventing allergies and runaway immune response. It also has mental effects, affecting mood and memory formation. Symptoms of too little cortisol may include fatigue, dizziness (especially upon standing), nausea, fever, weight loss, muscle weakness, joint pain, mood changes, and the darkening of regions of the skin.
The danger of taking too much corticosteroid may include insulin resistance, a decrease in lean body mass, increase in fat accumulation, and decrease in bone mineral density. It is also immunosuppressive, and may cause tissue breakdown (catabolism) and gastritis. Adverse effects increase with dose and duration of use.
Glucocorticosteroids have been found to have independent anti-cancer activity (see this link). The effect is short-lived as resistance eventually arises. It is also given to mitigate some of the side effects of chemotherapy like emesis/nausea and peripheral edema.
Attard et al. conducted a randomized clinical trial among men taking 1000 mg/day abiraterone for metastatic castration-resistant prostate cancer at 22 hospitals in 5 countries in 2013-2014.
- 41 received it with prednisone 5mg bid (P5 bid)
- 41 received it with prednisone 5 mg qd (P5 qd)
- 40 received it with prednisone 2.5 mg bid (P2.5 bid)
- 42 received it with dexamethasone 0.5 mg qd (D0.5 qd)
The primary outcome measured was mineralocorticoid excess through 24 weeks of treatment as indicated by elevated blood pressure or a blood test for low potassium (hypokalemia). They also measured serum levels of ACTH, which gets elevated if there is not enough glucocorticoid. For side effects of too much glucocorticoid, they measured insulin resistance, loss of lean body mass, gain of body fat, and loss of bone mineral density. For the benefits, they measured suppression of androgen precursors, the % of patients in whom PSA declined by at least 50%, the duration of radiographic progression-free survival, and the patient-reported change in quality of life.
|
P5 bid
|
P5 qd
|
P2.5 bid
|
D0.5 qd
|
Mineralocorticoid excess
|
29%
|
63%
|
40%
|
30%
|
(95% confidence range)
|
17%-46%
|
47%-77%
|
26%-56%
|
17%-46%
|
Grade 3 hypertension
|
7%
|
22%
|
13%
|
7%
|
Grade 3 hypokalemia
|
0%
|
7%
|
0%
|
0%
|
Change in ACTH (pmol/L)
|
-1.1
|
9.0
|
4.0
|
-1.8
|
Change in fasting serum insulin (insulin resistance)
|
Not statistically significant
|
Not statistically significant
|
Not statistically significant
|
significant
|
Change in lean body mass
|
-6%
|
-3%
|
-6%
|
Not statistically significant
|
Change in total body fat
|
12%
|
Not statistically significant
|
Not statistically significant
|
19%
|
Change in bone mineral density
|
Not statistically significant
|
Not statistically significant
|
Not statistically significant
|
-2%
|
Androgen precursor suppression
|
-81%
|
Not statistically significant
|
Not statistically significant
|
-88%
|
PSA declined by ≥ 50%
|
63%
|
78%
|
60%
|
88%
|
Radiographic Progression-free survival
|
18.5 months
|
15.3 months
|
12.8 months
|
26.6 months
|
Quality of Life change
|
Not statistically significant
|
Not statistically significant
|
Not statistically significant
|
Not statistically significant
|
Although sample sizes were not large enough to directly compare the treatments, the data suggest that P5 bid and D0.5 qd do a good job of preventing mineralocorticoid excess, whereas P5 qd does not. P5 bid and D0.5 qd seem to cause body changes. D0.5 qd seems to have superior oncological effectiveness.
There was tremendous individual variation. It seems prudent to start with the prescribed dose (P5 bid) and monitor body changes, or to start at the lower dose (P5 qd) and to monitor blood pressure and potassium levels.
In a retrospective study, Gill et al. found that castration-resistant men at Huntsman Cancer Center who refused prednisone suffered no worse from the syndrome of mineralocorticoid excess when given 50 mg/day Inspra (eplerenone - an aldosterone antagonist) compared to men who used 10 mg/day prednisone. They also lost weight, perhaps water-weight. Patients taking 10 mg/day of prednisone may wish to discuss this alternative.