Table 2.

Urinary cortisol metabolites and ratios in controls and patients receiving dual-release hydrocortisone and 3-times-daily hydrocortisone

ControlsPatientsAdjusted P
TID-HCDR-HCDifference TID-HC–DR-HCControls vs TID-HCaControls vs DR-HCaTID-HC vs DR-HCb
Steroids, μg/24 h
UFF48 (36 to 66)149 (93 to 239)84 (56 to 127)59 (26 to 125)< .001< .001< .001
THF1259 (838 to 1615)2558 (1758 to 3178)1617 (1229 to 2128)913 (425 to 1360)< .001.02< .001
5α-THF1000 (553 to 1481)1202 (755 to 1891)859 (473 to 1334)280 (99 to 466).3.001< .001
α-Cortol242 (177 to 317)271 (228 to 366)181 (139 to 256)101 (38 to 158).77< .001< .001
β-Cortol408 (259 to 574)352 (229 to 526)285 (200 to 650)19 (–75 to 110).85.92.74
UFE76 (60 to 100)225 (156 to 280)144 (97 to 195)66 (25 to 124)< .001< .001< .001
THE2364 (1735 to 3231)2445 (1995 to 3142)1817 (1398 to 2291)656 (151 to 1214).07< .001< .001
α-Cortolone966 (714 to 1306)755 (573 to 905)534 (399 to 713)193 (75 to 336)< .001< .001< .001
β-Cortolone532 (372 to 698)420 (293 to 539)327 (222 to 460)92 (–5 to –168)< .001< .001< .001
6β-OH-F106 (81 to 154)213 (121 to 378)99 (68 to 185)86 (49 to 175)< .001.8< .001
TCM6850 (4930 to 9159)8825 (6838 to 10 888)6380 (4421 to 7874)2337 (1239 to 4112).52.004< .001
Steroids ratio
UFE/UFF1.56 (1.32 to 1.84)1.41 (1.14 to 1.59)1.64 (1.37 to 1.97)–0.24 (–0.47 to –0.07)< .001.85< .001
(THF + 5α-THF)/THE0.89 (0.74 to 1.09)1.38 (1.2 to 1.75)1.39 (1.05 to 1.62)0.09 (–0.04 to 0.37)< .001< .001.003
THF/5α-THF1.26 (0.93 to 1.71)2.27 (1.28 to 3.34)1.98 (1.30 to 3.549)0.02 (–0.21 to 0.40)< .001< .001.32
Cortols/THF0.50 (0.42 to 0.67)0.28 (0.22 to 0.34)0.33 (0.24 to 0.44)–0.06 (–0.17 to –0.01)< .001< .001< .001
Cortolones/THE0.62 (0.53 to 0.72)0.45 (0.4 to 0.56)0.47 (0.4 to 0.58)–0.01 (–0.04 to 0.02)< .001< .001.12
α-Cortol/THF0.20 (0.17 to 0.25)0.12 (0.1 to 0.14)0.11 (0.1 to 0.14)–0.00 (–0.01 to 0.01)< .001< .001.74
α-Cortolone/THE0.41 (0.33 to 0.48)0.29 (0.25 to 0.34)0.28 (0.24 to 0.36)–0.01 (–0.01 to 0.03)< .001< .001.3
β-Cortol/THF0.29 (0.23 to 0.42)0.14 (0.11 to 0.21)0.19 (0.14 to 0.35)–0.05 (–0.16 to –0.01)< .001.067< .001
β-Cortolone/THE0.21 (0.18 to 0.25)0.16 (0.14 to 0.2)0.17 (0.15 to 0.23)–0.01 (–0.03 to 0.00).41.7< .001
ControlsPatientsAdjusted P
TID-HCDR-HCDifference TID-HC–DR-HCControls vs TID-HCaControls vs DR-HCaTID-HC vs DR-HCb
Steroids, μg/24 h
UFF48 (36 to 66)149 (93 to 239)84 (56 to 127)59 (26 to 125)< .001< .001< .001
THF1259 (838 to 1615)2558 (1758 to 3178)1617 (1229 to 2128)913 (425 to 1360)< .001.02< .001
5α-THF1000 (553 to 1481)1202 (755 to 1891)859 (473 to 1334)280 (99 to 466).3.001< .001
α-Cortol242 (177 to 317)271 (228 to 366)181 (139 to 256)101 (38 to 158).77< .001< .001
β-Cortol408 (259 to 574)352 (229 to 526)285 (200 to 650)19 (–75 to 110).85.92.74
UFE76 (60 to 100)225 (156 to 280)144 (97 to 195)66 (25 to 124)< .001< .001< .001
THE2364 (1735 to 3231)2445 (1995 to 3142)1817 (1398 to 2291)656 (151 to 1214).07< .001< .001
α-Cortolone966 (714 to 1306)755 (573 to 905)534 (399 to 713)193 (75 to 336)< .001< .001< .001
β-Cortolone532 (372 to 698)420 (293 to 539)327 (222 to 460)92 (–5 to –168)< .001< .001< .001
6β-OH-F106 (81 to 154)213 (121 to 378)99 (68 to 185)86 (49 to 175)< .001.8< .001
TCM6850 (4930 to 9159)8825 (6838 to 10 888)6380 (4421 to 7874)2337 (1239 to 4112).52.004< .001
Steroids ratio
UFE/UFF1.56 (1.32 to 1.84)1.41 (1.14 to 1.59)1.64 (1.37 to 1.97)–0.24 (–0.47 to –0.07)< .001.85< .001
(THF + 5α-THF)/THE0.89 (0.74 to 1.09)1.38 (1.2 to 1.75)1.39 (1.05 to 1.62)0.09 (–0.04 to 0.37)< .001< .001.003
THF/5α-THF1.26 (0.93 to 1.71)2.27 (1.28 to 3.34)1.98 (1.30 to 3.549)0.02 (–0.21 to 0.40)< .001< .001.32
Cortols/THF0.50 (0.42 to 0.67)0.28 (0.22 to 0.34)0.33 (0.24 to 0.44)–0.06 (–0.17 to –0.01)< .001< .001< .001
Cortolones/THE0.62 (0.53 to 0.72)0.45 (0.4 to 0.56)0.47 (0.4 to 0.58)–0.01 (–0.04 to 0.02)< .001< .001.12
α-Cortol/THF0.20 (0.17 to 0.25)0.12 (0.1 to 0.14)0.11 (0.1 to 0.14)–0.00 (–0.01 to 0.01)< .001< .001.74
α-Cortolone/THE0.41 (0.33 to 0.48)0.29 (0.25 to 0.34)0.28 (0.24 to 0.36)–0.01 (–0.01 to 0.03)< .001< .001.3
β-Cortol/THF0.29 (0.23 to 0.42)0.14 (0.11 to 0.21)0.19 (0.14 to 0.35)–0.05 (–0.16 to –0.01)< .001.067< .001
β-Cortolone/THE0.21 (0.18 to 0.25)0.16 (0.14 to 0.2)0.17 (0.15 to 0.23)–0.01 (–0.03 to 0.00).41.7< .001

Results are presented as median (interquartile range).

Abbreviations: 5α-THF, 5α-tetrahydrocortisol; 6β-OH-F, 6β-hydroxy-cortisol; DR-HC, dual-release hydrocortisone; TCM, total cortisol metabolites; THE, tetrahydrocortisone; THF, tetrahydrocortisol; TID-HC, 3-times-daily hydrocortisone; UFE, urinary free cortisone; UFF, urinary free cortisol.

a  P value adjusted for age, sex, and weight using logistic regression.

bPeriod-adjusted P value.

Table 2.

Urinary cortisol metabolites and ratios in controls and patients receiving dual-release hydrocortisone and 3-times-daily hydrocortisone

ControlsPatientsAdjusted P
TID-HCDR-HCDifference TID-HC–DR-HCControls vs TID-HCaControls vs DR-HCaTID-HC vs DR-HCb
Steroids, μg/24 h
UFF48 (36 to 66)149 (93 to 239)84 (56 to 127)59 (26 to 125)< .001< .001< .001
THF1259 (838 to 1615)2558 (1758 to 3178)1617 (1229 to 2128)913 (425 to 1360)< .001.02< .001
5α-THF1000 (553 to 1481)1202 (755 to 1891)859 (473 to 1334)280 (99 to 466).3.001< .001
α-Cortol242 (177 to 317)271 (228 to 366)181 (139 to 256)101 (38 to 158).77< .001< .001
β-Cortol408 (259 to 574)352 (229 to 526)285 (200 to 650)19 (–75 to 110).85.92.74
UFE76 (60 to 100)225 (156 to 280)144 (97 to 195)66 (25 to 124)< .001< .001< .001
THE2364 (1735 to 3231)2445 (1995 to 3142)1817 (1398 to 2291)656 (151 to 1214).07< .001< .001
α-Cortolone966 (714 to 1306)755 (573 to 905)534 (399 to 713)193 (75 to 336)< .001< .001< .001
β-Cortolone532 (372 to 698)420 (293 to 539)327 (222 to 460)92 (–5 to –168)< .001< .001< .001
6β-OH-F106 (81 to 154)213 (121 to 378)99 (68 to 185)86 (49 to 175)< .001.8< .001
TCM6850 (4930 to 9159)8825 (6838 to 10 888)6380 (4421 to 7874)2337 (1239 to 4112).52.004< .001
Steroids ratio
UFE/UFF1.56 (1.32 to 1.84)1.41 (1.14 to 1.59)1.64 (1.37 to 1.97)–0.24 (–0.47 to –0.07)< .001.85< .001
(THF + 5α-THF)/THE0.89 (0.74 to 1.09)1.38 (1.2 to 1.75)1.39 (1.05 to 1.62)0.09 (–0.04 to 0.37)< .001< .001.003
THF/5α-THF1.26 (0.93 to 1.71)2.27 (1.28 to 3.34)1.98 (1.30 to 3.549)0.02 (–0.21 to 0.40)< .001< .001.32
Cortols/THF0.50 (0.42 to 0.67)0.28 (0.22 to 0.34)0.33 (0.24 to 0.44)–0.06 (–0.17 to –0.01)< .001< .001< .001
Cortolones/THE0.62 (0.53 to 0.72)0.45 (0.4 to 0.56)0.47 (0.4 to 0.58)–0.01 (–0.04 to 0.02)< .001< .001.12
α-Cortol/THF0.20 (0.17 to 0.25)0.12 (0.1 to 0.14)0.11 (0.1 to 0.14)–0.00 (–0.01 to 0.01)< .001< .001.74
α-Cortolone/THE0.41 (0.33 to 0.48)0.29 (0.25 to 0.34)0.28 (0.24 to 0.36)–0.01 (–0.01 to 0.03)< .001< .001.3
β-Cortol/THF0.29 (0.23 to 0.42)0.14 (0.11 to 0.21)0.19 (0.14 to 0.35)–0.05 (–0.16 to –0.01)< .001.067< .001
β-Cortolone/THE0.21 (0.18 to 0.25)0.16 (0.14 to 0.2)0.17 (0.15 to 0.23)–0.01 (–0.03 to 0.00).41.7< .001
ControlsPatientsAdjusted P
TID-HCDR-HCDifference TID-HC–DR-HCControls vs TID-HCaControls vs DR-HCaTID-HC vs DR-HCb
Steroids, μg/24 h
UFF48 (36 to 66)149 (93 to 239)84 (56 to 127)59 (26 to 125)< .001< .001< .001
THF1259 (838 to 1615)2558 (1758 to 3178)1617 (1229 to 2128)913 (425 to 1360)< .001.02< .001
5α-THF1000 (553 to 1481)1202 (755 to 1891)859 (473 to 1334)280 (99 to 466).3.001< .001
α-Cortol242 (177 to 317)271 (228 to 366)181 (139 to 256)101 (38 to 158).77< .001< .001
β-Cortol408 (259 to 574)352 (229 to 526)285 (200 to 650)19 (–75 to 110).85.92.74
UFE76 (60 to 100)225 (156 to 280)144 (97 to 195)66 (25 to 124)< .001< .001< .001
THE2364 (1735 to 3231)2445 (1995 to 3142)1817 (1398 to 2291)656 (151 to 1214).07< .001< .001
α-Cortolone966 (714 to 1306)755 (573 to 905)534 (399 to 713)193 (75 to 336)< .001< .001< .001
β-Cortolone532 (372 to 698)420 (293 to 539)327 (222 to 460)92 (–5 to –168)< .001< .001< .001
6β-OH-F106 (81 to 154)213 (121 to 378)99 (68 to 185)86 (49 to 175)< .001.8< .001
TCM6850 (4930 to 9159)8825 (6838 to 10 888)6380 (4421 to 7874)2337 (1239 to 4112).52.004< .001
Steroids ratio
UFE/UFF1.56 (1.32 to 1.84)1.41 (1.14 to 1.59)1.64 (1.37 to 1.97)–0.24 (–0.47 to –0.07)< .001.85< .001
(THF + 5α-THF)/THE0.89 (0.74 to 1.09)1.38 (1.2 to 1.75)1.39 (1.05 to 1.62)0.09 (–0.04 to 0.37)< .001< .001.003
THF/5α-THF1.26 (0.93 to 1.71)2.27 (1.28 to 3.34)1.98 (1.30 to 3.549)0.02 (–0.21 to 0.40)< .001< .001.32
Cortols/THF0.50 (0.42 to 0.67)0.28 (0.22 to 0.34)0.33 (0.24 to 0.44)–0.06 (–0.17 to –0.01)< .001< .001< .001
Cortolones/THE0.62 (0.53 to 0.72)0.45 (0.4 to 0.56)0.47 (0.4 to 0.58)–0.01 (–0.04 to 0.02)< .001< .001.12
α-Cortol/THF0.20 (0.17 to 0.25)0.12 (0.1 to 0.14)0.11 (0.1 to 0.14)–0.00 (–0.01 to 0.01)< .001< .001.74
α-Cortolone/THE0.41 (0.33 to 0.48)0.29 (0.25 to 0.34)0.28 (0.24 to 0.36)–0.01 (–0.01 to 0.03)< .001< .001.3
β-Cortol/THF0.29 (0.23 to 0.42)0.14 (0.11 to 0.21)0.19 (0.14 to 0.35)–0.05 (–0.16 to –0.01)< .001.067< .001
β-Cortolone/THE0.21 (0.18 to 0.25)0.16 (0.14 to 0.2)0.17 (0.15 to 0.23)–0.01 (–0.03 to 0.00).41.7< .001

Results are presented as median (interquartile range).

Abbreviations: 5α-THF, 5α-tetrahydrocortisol; 6β-OH-F, 6β-hydroxy-cortisol; DR-HC, dual-release hydrocortisone; TCM, total cortisol metabolites; THE, tetrahydrocortisone; THF, tetrahydrocortisol; TID-HC, 3-times-daily hydrocortisone; UFE, urinary free cortisone; UFF, urinary free cortisol.

a  P value adjusted for age, sex, and weight using logistic regression.

bPeriod-adjusted P value.

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