Table 2. Incidences of secondary adrenal insufficiency after ACTH therapy confirmed using adrenal stimulation tests.
| Study | Ross et al.11 | Perheentupa et al.12 | Rao and Willis13 | Mytinger et al.7 | Sakaguchi et al.8 | Doré-Brabant et al.14 | Bistritzer et al.2 |
Abe et al.15 |
| Number of patients | 5 | 10 | 9 | 9 | 35 | 12 | 5 | 6 |
| Secondary adrenal insufficiency | 1 (20%) | #1 | 5 (56%) | 1 (11%) | 4 (11%) | 8 (67%) | 0 | 1 (17%) |
| Baseline characteristics | ||||||||
| Age | median 20 mo | mean 9 mo#2 | median 5 mo | median 6 mo#3 | median 8 mo #4 |
mean 8 mo#4, 5 | median 6.5 mo#4 | median 1 yr 3 mo |
| Age range | 8 mo to 8 yr | 5 to 22 mo | 7 wks to 16 mo | 5 to 12 mo | 2 to 25 mo | 1.6 to 21.1 mo | 4 to 9 mo | 4 mo to 5 yr 2 mo |
| Treatment | natural ACTH | synthetic ACTH | natural ACTH | natural ACTH | synthetic ACTH | synthetic ACTH | synthetic ACTH | synthetic ACTH |
| Dose | 80 IU/day | 150 IU/m2/day | 1.9 mg/m2 every other day#6 | 30 IU/day | ||||
| Dose range | 1.1 to 9 IU/kg/day | 6.6 to 13.1 IU/kg/day | 20 to 40 IU/day | 0.01 to 0.0125 mg/kg/day | 2.1 to 5 IU/kg | 0.0125 to 0.025 mg/kg/day | ||
| Duration | 1 to 3 mo | 42 days | 30 to 66 days | 2 wks#7 | 2 wks#8 | mean; 50 days, SD; 22 days | 2 wks#9 | 2 wks#10 |
| Adrenal stimulation test | ||||||||
| Stimulation agents | insulin | vasopressin + ACTH | metyrapone | glucagon or ACTH#11 | CRH | ACTH | low dose ACTH | CRH |
| Diagnostic criterion for adrenocortical insufficiency |
no description of peak F | #12 | peak11-deoxycortisol < 7 mg/dL | peak F < 18 mg/dL | peak F < 15 mg/dL | no description#13 | peak F < 18 mg/dL | peak F < 20 mg/dL |
| Timing of testing from ACTH therapy completion |
immediately#14 | 3 days, 1 and 2 wks | 2 days | mean 8.9 wks#15 | median 10 days | mean 49 days | median 2 days | |
| range; 3 to 33 days | range; 2 to 192 days | range; -15 to 11 days | range; 3 to 16 days |
#1: No data of individual morbidity. Two weeks after ACTH therapy, serum F 120 minutes after stimulation was low in five out of seven (71%).
#2: Ages on admission.
#3: Corrected ages at initiation of ACTH therapy.
#4: Ages at initiation of ACTH therapy.
#5: Including patients treated with ACTH alone, corticosteroid alone and combined treatment (ACTH, corticosteroid).
#6: Total cumulative dose, mean (SD); 19.31 (9.82) mg/m2.
#7: Followed by a tapering over 15 days.
#8: Followed by a tapering of two weeks.
#9: With weekly downward titration.
#10: Then on alternate days for 14 days.
#11: Two and seven patients were evaluated by means of glucagon stimulation tests and ACTH stimulation tests, respectively.
#12: Peak F; < 23.9 μg/dl after vasopressin stimulation or < 29.8 μg/dl after ACTH stimulation.
#13: Peak F of the patients diagnosed as having adrenal insufficiency was median 200 nmol/L, range 0 to 481 nmol/L.
#14: Within 48 hours after tapered withdrawal of ACTH.
#15: Median after 9 wks, range; 2 to 18 wks.
F, cortisol.