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Table 1 Summary of selected studies

From: Adrenal fatigue does not exist: a systematic review

First Author & Reference Year of Publication Number of Patients Population Questionnaire Tests Results Comments
McLennan [21] 2016 257 H/B Maslach HCC Nl  
Schmidt [69] (part 1) 2016 265 Breast Cancer FAQ DAC, CAR, SCR, NSC ↑NSC, ↑AUC, Nl CAR, Nl DAC, ↓SCR Pts. mostly on chemotherapy (ChTx); schemes not specified. No controls, only correlation between fatigue levels and tests. ChTx related to worse fatigue. Initial tests performed during, w/ or w/o ChTx.
Schmidt [69] (part 2) 2016 265 Breast Cancer FAQ DAC, CAR, SCR, NSC ↑AUC, ↑CAR, ↑NSC, ↑SCR, Nl DAC Second test of the study, performed after 14 weeks of procedures.
Sjors [25] 2015 220 H/B SMBQ DAC, CAR ↓CAR, ↑DAC Results normalized after adjustment of anti-depressive use; SCR results not provided
Oosterholt [28] 2015 91 H/B Maslach DAC, CAR, SCR, AUC, CAR 60 min Nl SCR, ↓CAR, Nl AUC, Nl CAR 60 min, ↓DAC Control of variations did not change results
De Vente [22] 2015 95 H/B Acute Psychosocial Stressor diagnosis MSC, MST Nl MSC, Nl MST MST: Nl (women), reduced (men); MSC: Nl (men), reduced (women). Mental arithmetic and public speech stressors also performed
Lennartsson [24] 2015 56 H/B DCSRD; exclusion w/ SEQ DHEA-S; ACTH; ACTH and DHEA-S post-TSST (TSST stress test performed) ↓DHEA-S, ↓post-TSST DHEA-S, Nl ACTH, Nl post-TSST ACTH  
Tao [23] 2015 171 H/B Maslach MSC, ACTH ↑ACTH, ↑MSC  
Jonsson [29] 2015 51 H/B SMBQ MSC, MST Nl MSC, ↓MST  
Lennartsson [27] 2015 56 H/B DCSRD and SMBQ MSC, MST, ACTH, ACTH post-TSST (TSST stress test performed) Nl MSC, Nl MST, Nl ACTH, Nl post-TSST ACTH Severe BO: lower ACTH, cortisol response to TSST vs controls, whereas low BO: higher ACTH, cortisol responses vs controls
Schmaling [26] 2015 62 Healthy ADAS AUC, SCR ↓AUC, ↓SCR 31 couples studied, one of which had chronic fatigue (but not CFS)
Sveinsdottir [68] 2015 1150 Chronic Lombalgia CFQ DAC, CAR, SCR, NSC Nl DAC, Nl CAR, Nl NSC, Nl SCR **Colocar como SAUDÁVEL – porque é só lombalgia (increased CAR in Low back pain)
Powell [67] 2015 76 Multiple Sclerosis CFQ DAC, CAR, SCR ↓DAC, ↑CAR, Nl SCR Sleep disorders excluded; adjusted for depressive symptoms; NSC not published. Multiple sclerosis had increased awakening cortisol and decreased CAR
Cruz [70] 2015 43 Breast cancer BFI and CFQ MSC, DHEA-S Nl MSC, Nl DHEA-S Pts undergoing ChTx included anthracyclines
Marchand [31] 2014 1043 H/B Maslach DAC, CAR, SCR, NSC ↑DAC, ↓CAR, ↑SCR, ↓NSC Only BO; Groups of severe distress or depression not included
Aggarwal [30] 2014 227 Healthy CFQ MSC, NSC, 0.25 mg DST, DHEA-S Nl MSC, Nl NSC, Nl 0.25 mg DST, ↓DHEA-S Evaluation of chronic, widespread pain, chronic orofacial pain, chronic fatigue (but not CFS), irritable bowel syndrome
Tell D [71] 2014 130 Breast cancer MFI DAC, CAR, SCR, NSC ↓CAR, ↓SCR, ↑DAC, ↑NSC Post-surgery breast cancer, regardless of ChTx. Not adjusted to sleeping patterns
Wolfram [32] 2013 53 H/B Maslach MSC, 1 mcg CST, DST/CRH test (1.5 mg DST + 100 mcg CRH) Nl MSC, ↓post-1 mcg ACTH, Nl ACTH and cortisol DST-CRH High over-commitment present blunted serum and salivary cortisol and ACTH responses to DST-CRH test
Klaassen [33] 2013 27 Healthy MP (Beck & Luine, 2010) and Stress Tasks (Wang, 2006) MSC, post-stress Nl MSC, Nl post-stress A complex test sequence was performed but not reproduced
Eek [34] 2012 581 Healthy SOFI-20 DAC, CAR, NSC, SCR, MSC Nl DAC, Nl CAR, Nl NSC, Nl SCR, Nl MSC Women: reduced awakening, increased CAR, increased SCR; Men: increased awakening and reduced CAR – when fatigued
Sjors [35] 2012 247 H/B DCSRD and SMBQ DAC, 15 min CAR Nl DAC, Nl 15 min CAR  
Rahman [54] 2011 30 CFS Previous Dx – No questionnaire MSC, SCR, NSC Nl MSC, Nl SCR, Nl NSC  
Moya-Albiol [37] 2010 64 H/B Maslach DAC, CAR Nl DAC, Nl CAR  
Kumari [38] 2009 4,299 Healthy SF-36 DAC, CAR, NSC, SCR ↓DAC, ↓CAR, ↑NSC, ↓SCR Adjusted for WC, BMI, sleep duration, CVD medication, depressive symptoms, smoking, alcohol intake provides Nl awakening but lower SCR
Osterberg [39] 2009 304 H/B Maslach DAC, CAR, NSC, SCR Nl DAC, Nl CAR, ↓NSC, ↑SCR 0.5 mg DST was not compared to controls
Wingenfeld [41] 2009 279 H/B Maslach and Maastricht AUC, SCR Nl AUC, Nl SCR DAC and CAR not done; conclusions different from results. For AUC, Low BO: Nl, moderate: increased, severe: decreased
Rydstedt [40] 2009 76 Healthy NRWS DAC, NSC Nl DAC, Nl NSC  
Papadopoulos [55] 2009 38 CFS CFQ and SF-36 MSC, AUC, morning AUC, 0,5 mg DST ↑MSC, ↑AUC, ↑MAUC, Nl 0.5 mg DST Data on absolute cortisol levels at each point not published. DST reduction evaluated by percent reduction.
Bay [72] 2009 75 Post traumatic brain injury POMS AUC Nl AUC Correlation between brain injury-related fatigue level and cortisol AUC. Basal and NSC results not reported; SCR not evaluated.
Sudhaus [73] 2009 43 Chronic Lombalgia MFI DAC, CAR, MAUC ↓CAR, Nl DAC, Nl MAUC (correlation between fatigue levels among low back pain subjects)  
Lindeberg [36] 2008 78 Healthy SF-36 DAC, CAR, NSC, SCR Nl DAC, ↓CAR, Nl NSC, ↓SCR  
Sertoz [42] 2008 72 H/B Maslach Basal and post 1.0 mcg DST cortisol Nl basal cortisol and 1.0 mg DST  
Bellingrath [43] 2008 101 H/B Maslach and Maastricht DAC, CAR, NSC, SCR, 0.25 mg DST Nl DAC, Nl CAR, Nl NSC, Nl SCR, ↓0.25 mg DST  
Nater [57] 2008 185 CFS SF-36 and MFI DAC, CAR, MAUC Nl DAC, Nl CAR, ↓MAUC  
Torres-Harding [56] 2008 108 CFS FSE AUC, SCR Nl AUC, Nl SCR Multiple psychological tests performed. Data on NSC, basal and CAR not published.
Sonnenschein [45] 2007 42 H/B Maslach CAR, 0.5 mg DST, DHEA-S Nl CAR, Nl 0.5 mg DST, Nl DHEA-S Adjusted for depression, sleep quality. Awakening levels and each level graphics not available
Harris [44] 2007 44 Healthy SF-36 DAC, CAR, NSC, SCR Nl DAC, Nl CAR, Nl NSC, Nl SCR Other aspects also correlated: complains, job stress and demand, QOL and coping. Adjusted for coffee and tobacco.
Langelaan [46] 2006 55 H/B Maslach DAC, CAR, 0.5 mg DST, DHEA-S Nl DAC, Nl CAR, Nl 0.5 mg DST, Nl DHEA-S Engaged work also compared and had stronger suppression in DST
Mommersteeg [47] 2006 109 Healthy NC-WHO DAC, CAR, 0.5 mg DST, SCR, AUC, NSC Nl DAC, Nl CAR, Nl NSC, Nl SCR, Nl 0.5 mg DST, Nl AUC  
Barroso [74] 2006 40 HIV HRFS MSC, NSC ↓MSC, ↑NSC  
Jerjes [58] 2006 80 CFS CFQ UFC, TCM ↓UFC, Nl TCM  
Grossi [48] 2005 64 H/B SMBQ DAC, CAR ↓DAC, ↑CAR Groups were high x moderate x low BO score; correlation was significant
Segal [59] 2005 40 CFS No questionnaire MSC, 1 mcg CST ↓ MSC, ↓1 mcg CST DHEA-S collected only in CFS. No questionnaires used.
Jerjes [60] 2005 35 CFS CFQ MSC, SCR, NSC, AUC ↓MSC, ↓SCR, ↓AUC ↓, Nl NSC  
Bower [75] 2005 29 Breast cancer SF-36 DAC, AUC, SCR, NSC ↑AUC, ↓SCR, Nl DAC, ↑NSC Post-ChTx (regardless of time) complete cancer remission and exclusion of other disorders
McLean [76] 2005 55 Fybro-mialgia SF-36 DAC, 60 min CAR, SCR, AUC, NSC Nl DAC, Nl 60 min CAR, Nl SCR, Nl AUC, Nl NSC (correlation between fatigue levels among FMG subjects) FMG subjects presented Nl DAC and CAR, as controls.
Roberts [62] 2004 92 CFS CFQ and SF-36 DAC, CAR, MAUC Nl DAC, ↓CAR, ↓MAUC  
Crofford [61] 2004 72 CFS/FMG POMS ACTH, MSC, SCR, NSC, AUC Nl ACTH, Nl SCR, Nl NSC, ↓AUC, Nl MSC Tests performed in: CFS, FMG and CFS + FMG; FMG w/o fatigue had Nl AUC and increased BMC levels
Moch [50] 2003 16 H/B Maslach UFC, DHEA-S, ACTH, MSC ↓UFC, Nl DHEA-S, Nl ACTH, ↓MSC Only women; longitudinal evaluation – Nl initial cortisol.
De Vente [49] 2003 45 H/B Maslach DAC, MSC, post-TSST ↑DAC, ↑MSC, Nl post-TSST  
Gaab [63] 2002 42 CFS MFI DAC, CAR, SCR, 0.5 mg DST ↓0.5 mg DST, Nl AUC, Nl CAR, Nl DAC, Nl SCR, Nl NSC CAR also performed at 15, 45 and 60 min.
Dekkers [77] 2000 53 Rheumatoid Arthritis MFI DAC, CAR, SCR, AUC Nl AUC, Nl SCR Nl, ↓DAC, ↑CAR 5/25 subjects with RA taking prednisone (5–10 mg/d); RS subjects had smaller SCR, increased AM cortisol and decreased CAR. 15 and 45 min CAR also performed.
Melamed [51] 1999 111 H/B SMBQ and Maastricht MSC and 4 PM cortisol ↑MSC, Nl 4 PM cortisol  
Pruessner [52] 1999 66 Healthy Maslach DAC, CAR, 0.5 mg DST ↓DAC, ↓CAR, ↓0.5 mg DST 15 min and 60 min CAR also performed
Strickland [65] 1998 74 CFS Not specified/detailed MSC, NSC ↓NSC, Nl MSC Adjusted for depression
Young [66] 1998 45 CFS NC-WHO UFC, SCR, MSC, AUC Nl UFC, Nl SCR, Nl MSC, Nl AUC  
Scott [64] 1998 28 CFS Not specified (not detailed) MSC, ACTH, 100 mcg CRH cortisol stimulation Nl MSC, Nl ACTH, CRH stim test: ↓cortisol, ↓ACTH  
Raikkonen [53] 1996 22 Healthy Not assessed 1 mcg CST, DST (non specified), OGTT, MSC, ACTH, cortisol/ACTH ratio ↑Cortisol/ACTH ratio; ↑CST, Nl DST, Nl OGTT, Nl MSC, Nl ACTH Full article not assessed – not in PUBMED or other database
  1. Questionnaires: SMBQ shirom-melamed burnout questionnaire, BFI brief fatigue inventory, CFQ chalder fatigue questionnaire, Maslach maslach burnout inventory, SF-36 short form health survey 36, NC-WHO neurasthenia criteria, DCSRD diagnosis criteria of stress-related exhaustion disorder, SEQ stress-energy questionnaire, ADAS, abbreviated dyadic adjustment scale, MFI multidimensional fatigue inventory, FAQ fatigue assessment questionnaire, MP memory performance, POMS profile of mood states, Stress Tasks, FSE fatigue severity scale, SOFI Swedish occupational fatigue inventory, Maastricht Maastricht vital exhaustion questionnaire, NRWS need for recovery from work scale, HRFS HIV-related fatigue scale, WC waist circumference
  2. Other abbreviations: CFS chronic fatigue syndrome, H/B healthy/burnout, 24 h-UFC 24-h urinary free cortisol, FMG fibromyalgia; ↑: Increased or elevated; ↓: Decreased or reduced; →: Unchanged; Nl: Normal