Table 2.

Summary of included studies assessing cortisol in participants with SCD

Study (year)CountryAge, ySample, nGenotypesAssay typeCollection detailsComparisons and correlatesStudy quality
Hair cortisol 
Hollister et al28 (2021) United States MSCD: 38.9 ± 11.9 SCD: 73 SCD: HbSS, HbSC, HbSβ0, HbSβ+ Enzyme immunoassay 3-cm sample cut from the posterior vertex of the head, as close to the scalp as possible; time and clinical condition not specified 
  • Disease severity

  • Hematological measures

  • Serum hormones

 
Salivary cortisol 
Kölbel et al29 (2022) England MSCD: 19.94 ± 4.8
Range: 9-29
Mcontrol: 19.02 ± 3.8
Range: 11-24 
SCD: 21
Control: 14 
SCD: HbSS
Control: HbAS, HbAA 
Enzyme immunoassay 4 samples during 1 weekday of the week: waking, 30 minutes after waking, afternoon (2 PM), evening (4 PM), and bedtime 
  • Control group 

  • Cortisol profiles

  • Sleep profiles

  • Cognitive domains

 
Serum cortisol 
Akinlade et al30 (2013)  Nigeria Range: 18-40 SCD: 60
Control: 30 
SCD: HbSS
Control: HbAA 
ELISA 1 sample collected in steady state in clinic or shortly after inpatient admission for VOC; time not specified 
  • Control group

  • VOC

 
Akinlade et al31 (2013) Nigeria Msteady: 27.1 ± 6.3
MVOC: 24.9 ± 4.9 
SCD: 60 SCD: HbSS ELISA 1 sample collected in steady state in clinic or shortly after hospital admission for VOC; time not specified 
  • Disease severity

 
Bashir et al32 (1993)  Jordan Range: 3-10 SCD: 21
Control: 22 
SCD: HbSS
Control: HbAA 
Radioimmunoassay 1 sample collected between 8 AM and 9 AM; clinical condition not specified 
  • Control group

 
El-Sonbaty et al33 (2016)  Saudi Arabia MSCD: 10.4 ± 2.7
Range: 6-16
Mcontrol: 9.7 ± 0.2
Range: 6-16 
SCD: 29
Control: 29 
SCD: HbSS
Control: not specified 
ELISA 1 sample collected at 7:30 AM;
clinical condition not specified 
Control group 
Hydroxyurea use
VOC frequency
Clinical and laboratory values 
Garadah et al34 (2016)  Bahrain MSCD: 21.2 ± 5.7
Range: 12-45
Mcontrol: 20.7 ± 5.8
Range: not specified 
SCD: 82
Control: 82 
SCD: HbSS
Control: not specified 
Chemiluminescence immunoassay Number of samples, clinical condition, environment, and time of day not specified 
  • Control group, 

  • Adrenal standard

  • Ferritin

 
Groom et al35 (1990) United States MSCD: 28.1 ± 3.6
Range: 22-34 
SCD: 9 SCD: not specified Solid phase radioimmunoassay 1 sample collected during hospital admission; time of day not specified 
  • Adrenal standard

 
Hagag et al36 (2015)  Egypt MSCD: 13 ± 2.9
Range: 5-17
Mcontrol: 11.7 ± 3.2
Range: 7-17 
SCD: 60
Control: 30 
SCD: HbSS
Control: not specified 
ECLIA 1 sample collected at baseline and 1 sample collected 1 hour after ACTH (synacthen or cosyntropin); time of day and clinical condition not specified 
  • Control group

  • ACTH stimulation

  • Ferritin

  • Iron

 
Soliman et al38 (1995)  Oman MSCD: 7.9 ± 1.1
Range: 5.7-11.5
Mcontrol: 8.1 ± 0.5
Range: 6-11 
SCD: 15
Control: 15 
Not specified Not specified 1 sample collected after an 8-hour overnight fast, followed by 1 sample 60 minutes after ACTH (synacthen) 
  • Control group 

  • ACTH stimulation

 
Soliman et al37 (1995)  Oman MSCD: 8.6 ± 2.9
Range: 4-10
Mcontrol: 7.6 ± 0.07
Range: 4-10 
SCD: 15
Control: 20 
Not specified Radioimmunoassay Sample collected between 8 and 9 AM(day of admission) after an 8-hour overnight fast and, 30, 60, 120, and 180 minutes after ACTH (glucagon) 
  • Control group 

  • ACTH stimulation

 
Solomon, et al39 (2012) United States§  “Adults,” age not specified SCD: 37 Not specified Not specified 1 sample from inpatient and outpatient laboratory values, with subanalyzes using morning samples (between 4 AM and 8 AM); cosyntropin stimulation tests performed on patients with low cortisol 
  • Adrenal standard

  • ACTH stimulation

 
Plasma cortisol 
Adams et al40 (2017) England§  Range: 17-77 SCD: 36 SCD: HbSS, HbSβ0, HbSOArab Not specified 1 sample collected in “early morning”; time and clinical condition not specified 
  • Adrenal standard

  • Opioid dose

 
el-Hazmi et al41 (1992)  Saudi Arabia Range: 4-50 SCD: 80
Control: 60 
SCD: HbSS
Control: not specified 
Radioimmunoassay 1 sample collected; clinical condition and time of day not specified 
  • Control group

  • Gender

  • Disease severity

 
el-Hazmi et al42 (1994)  Saudi Arabia Range: 2-15 SCD: 25
Control: 50 
SCD: HbSβ0
Control: HbAA 
Radioimmunoassay 1 sample collected at least 3 weeks after last transfusion; time of day not specified 
  • Control group

  • Gonadotropic hormones

 
Grewen et al43 (2012) United States§  Not specified SCD: 20 SCD: HbSS, HbSC Not specified Number of samples, time of day, and clinical condition not specified 
  • Pain intensity

  • Oxytocin

 
Osifo et al44 (1988)  Nigeria§  Range: 1-16 SCD: 36
Control1: 36
Control2: 36 
SCD: HbSS
Control1: HbAA
Control2: HbAS 
Radioimmunoassay 1 sample collected between 8 AM and 9 AM at clinic routine visit 
  • Control group

  • Adrenal standard

  • VOC

 
Rosenbloom et al45 (1980) United States Range: 20-30 SCD: 7
Control: 4 
SCD: HbSS HbSβ (+/0 unspecified)
Control: not specified 
Radioimmunoassay 1 sample collected in the morning (AM), followed by additional samples 30, 60, and 90 minutes after insulin. Additional sample 1 hour after Cortosyn. Clinical condition not specified 
  • Control group

  • VOC

  • ACTH stimulation

  • Insulin stimulation

 
Saad and Saad46 (1992)  Brazil MSCD: 25.5
Range: 18-38
Mcontrol: 28
Range: 22-35 
SCD: 14
Control: 16 
SCD: “SCA” unspecified
Control: not specificized 
Radioimmunoassay Sample collected between 8 and 9 AM, followed by samples collected 30, 60, and 120 minutes after ACTH (corticotropin); clinical condition not specified 
  • Control group

  • ACTH stimulation

 
Sobngwi et al47 (2018)  Camero-on MSCD: 28 ± 5
Range: >18
Mcontrol: 28 ± 5
Range: >18 
SCD: 10
Control: 10 
SCD: not specified
Control: HbAA 
Immunochemiluminescence Sample collected after overnight 12-hour fast and 60 minutes after synthetic ACTH (tetracosactide); clinical condition not specified 
  • Control group, 

  • ACTH stimulation

 
Study (year)CountryAge, ySample, nGenotypesAssay typeCollection detailsComparisons and correlatesStudy quality
Hair cortisol 
Hollister et al28 (2021) United States MSCD: 38.9 ± 11.9 SCD: 73 SCD: HbSS, HbSC, HbSβ0, HbSβ+ Enzyme immunoassay 3-cm sample cut from the posterior vertex of the head, as close to the scalp as possible; time and clinical condition not specified 
  • Disease severity

  • Hematological measures

  • Serum hormones

 
Salivary cortisol 
Kölbel et al29 (2022) England MSCD: 19.94 ± 4.8
Range: 9-29
Mcontrol: 19.02 ± 3.8
Range: 11-24 
SCD: 21
Control: 14 
SCD: HbSS
Control: HbAS, HbAA 
Enzyme immunoassay 4 samples during 1 weekday of the week: waking, 30 minutes after waking, afternoon (2 PM), evening (4 PM), and bedtime 
  • Control group 

  • Cortisol profiles

  • Sleep profiles

  • Cognitive domains

 
Serum cortisol 
Akinlade et al30 (2013)  Nigeria Range: 18-40 SCD: 60
Control: 30 
SCD: HbSS
Control: HbAA 
ELISA 1 sample collected in steady state in clinic or shortly after inpatient admission for VOC; time not specified 
  • Control group

  • VOC

 
Akinlade et al31 (2013) Nigeria Msteady: 27.1 ± 6.3
MVOC: 24.9 ± 4.9 
SCD: 60 SCD: HbSS ELISA 1 sample collected in steady state in clinic or shortly after hospital admission for VOC; time not specified 
  • Disease severity

 
Bashir et al32 (1993)  Jordan Range: 3-10 SCD: 21
Control: 22 
SCD: HbSS
Control: HbAA 
Radioimmunoassay 1 sample collected between 8 AM and 9 AM; clinical condition not specified 
  • Control group

 
El-Sonbaty et al33 (2016)  Saudi Arabia MSCD: 10.4 ± 2.7
Range: 6-16
Mcontrol: 9.7 ± 0.2
Range: 6-16 
SCD: 29
Control: 29 
SCD: HbSS
Control: not specified 
ELISA 1 sample collected at 7:30 AM;
clinical condition not specified 
Control group 
Hydroxyurea use
VOC frequency
Clinical and laboratory values 
Garadah et al34 (2016)  Bahrain MSCD: 21.2 ± 5.7
Range: 12-45
Mcontrol: 20.7 ± 5.8
Range: not specified 
SCD: 82
Control: 82 
SCD: HbSS
Control: not specified 
Chemiluminescence immunoassay Number of samples, clinical condition, environment, and time of day not specified 
  • Control group, 

  • Adrenal standard

  • Ferritin

 
Groom et al35 (1990) United States MSCD: 28.1 ± 3.6
Range: 22-34 
SCD: 9 SCD: not specified Solid phase radioimmunoassay 1 sample collected during hospital admission; time of day not specified 
  • Adrenal standard

 
Hagag et al36 (2015)  Egypt MSCD: 13 ± 2.9
Range: 5-17
Mcontrol: 11.7 ± 3.2
Range: 7-17 
SCD: 60
Control: 30 
SCD: HbSS
Control: not specified 
ECLIA 1 sample collected at baseline and 1 sample collected 1 hour after ACTH (synacthen or cosyntropin); time of day and clinical condition not specified 
  • Control group

  • ACTH stimulation

  • Ferritin

  • Iron

 
Soliman et al38 (1995)  Oman MSCD: 7.9 ± 1.1
Range: 5.7-11.5
Mcontrol: 8.1 ± 0.5
Range: 6-11 
SCD: 15
Control: 15 
Not specified Not specified 1 sample collected after an 8-hour overnight fast, followed by 1 sample 60 minutes after ACTH (synacthen) 
  • Control group 

  • ACTH stimulation

 
Soliman et al37 (1995)  Oman MSCD: 8.6 ± 2.9
Range: 4-10
Mcontrol: 7.6 ± 0.07
Range: 4-10 
SCD: 15
Control: 20 
Not specified Radioimmunoassay Sample collected between 8 and 9 AM(day of admission) after an 8-hour overnight fast and, 30, 60, 120, and 180 minutes after ACTH (glucagon) 
  • Control group 

  • ACTH stimulation

 
Solomon, et al39 (2012) United States§  “Adults,” age not specified SCD: 37 Not specified Not specified 1 sample from inpatient and outpatient laboratory values, with subanalyzes using morning samples (between 4 AM and 8 AM); cosyntropin stimulation tests performed on patients with low cortisol 
  • Adrenal standard

  • ACTH stimulation

 
Plasma cortisol 
Adams et al40 (2017) England§  Range: 17-77 SCD: 36 SCD: HbSS, HbSβ0, HbSOArab Not specified 1 sample collected in “early morning”; time and clinical condition not specified 
  • Adrenal standard

  • Opioid dose

 
el-Hazmi et al41 (1992)  Saudi Arabia Range: 4-50 SCD: 80
Control: 60 
SCD: HbSS
Control: not specified 
Radioimmunoassay 1 sample collected; clinical condition and time of day not specified 
  • Control group

  • Gender

  • Disease severity

 
el-Hazmi et al42 (1994)  Saudi Arabia Range: 2-15 SCD: 25
Control: 50 
SCD: HbSβ0
Control: HbAA 
Radioimmunoassay 1 sample collected at least 3 weeks after last transfusion; time of day not specified 
  • Control group

  • Gonadotropic hormones

 
Grewen et al43 (2012) United States§  Not specified SCD: 20 SCD: HbSS, HbSC Not specified Number of samples, time of day, and clinical condition not specified 
  • Pain intensity

  • Oxytocin

 
Osifo et al44 (1988)  Nigeria§  Range: 1-16 SCD: 36
Control1: 36
Control2: 36 
SCD: HbSS
Control1: HbAA
Control2: HbAS 
Radioimmunoassay 1 sample collected between 8 AM and 9 AM at clinic routine visit 
  • Control group

  • Adrenal standard

  • VOC

 
Rosenbloom et al45 (1980) United States Range: 20-30 SCD: 7
Control: 4 
SCD: HbSS HbSβ (+/0 unspecified)
Control: not specified 
Radioimmunoassay 1 sample collected in the morning (AM), followed by additional samples 30, 60, and 90 minutes after insulin. Additional sample 1 hour after Cortosyn. Clinical condition not specified 
  • Control group

  • VOC

  • ACTH stimulation

  • Insulin stimulation

 
Saad and Saad46 (1992)  Brazil MSCD: 25.5
Range: 18-38
Mcontrol: 28
Range: 22-35 
SCD: 14
Control: 16 
SCD: “SCA” unspecified
Control: not specificized 
Radioimmunoassay Sample collected between 8 and 9 AM, followed by samples collected 30, 60, and 120 minutes after ACTH (corticotropin); clinical condition not specified 
  • Control group

  • ACTH stimulation

 
Sobngwi et al47 (2018)  Camero-on MSCD: 28 ± 5
Range: >18
Mcontrol: 28 ± 5
Range: >18 
SCD: 10
Control: 10 
SCD: not specified
Control: HbAA 
Immunochemiluminescence Sample collected after overnight 12-hour fast and 60 minutes after synthetic ACTH (tetracosactide); clinical condition not specified 
  • Control group, 

  • ACTH stimulation

 

ECLIA, electrochemiluminescence immunoassay; ELISA, enzyme-linked immunosorbent assay; M, median.

Age-matched control group.

Included in quantitative meta-analysis.

Sex-matched control group.

§

Country of corresponding author’s institution listed because country of recruitment was not specified.

or Create an Account

Close Modal
Close Modal