Table 1.
Studies with AI/non-functioning AI and bone assessments: the analysis of criteria defining ACS (or SCS)—the studies are displayed in the order of publication [43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82]. Studied population [43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82].
| First Author Year of Publication Reference Number Study Design |
Studied Population (and Included Subgroups According to Each Study) Gender (F/M) Age (Years) |
|||
|---|---|---|---|---|
| Reincke 1992 [43] Prospective study |
N = 68 N1 = 8 with overt CS F/M = 8/0 Mean age: 39 ± 8 y (26–50 y) |
N2 = 8 with preclinical CS
F/M = 5/3 Mean age: 50 ± 15 y (25–71 y) |
N3 = 58 with NFAI
F/M = 37/21 Mean age: 59 ± 12 y (25–90 y) |
|
| Ambrosi 1995 [44] Case-control study |
N = 32 N1 = 32 with AI F/M = 23/9 Median age (women):49 y/median age (men): 67 y |
N2 = 4 with preclinical CS
F/M = 1/3 (42–72 y) |
N3 = 14 controls F/M = 8/6 (25–50 y) |
|
| Osella 1997 [45] Case-control study |
N = 22 N1 = 18 with CS F/M = 15/3 Median age: 36 y (15–64 y) |
N2 = 22 with AI
F/M = 13/9 Median age: 54.5 y (25–73 y) |
N3 = 22 controls Median age: 55 y (25–73 y) |
|
| Sartorio 1998 [46] Case-control study |
N = 53 N1 = 12 with CS F/M = 10/2 (21–46 y) |
N2 = 6 with preclinical CS
F/M = 2/4 (42–74 y ) |
N3 = 35 with AI F/M = 25/10 (34–73 y) | N4 = 28 controls (25–69 y) |
| Rossi 1999 [47] Prospective study |
N = 50 N1 = 50 with AI F/M = 29/21 mean age: 56.3 y (32–73 y) of these 12 with SCS = N2: F/M = 9/3 Mean age: 60.7 y (47–72 y) |
N3 = 107 controls F/M = 65/42 Mean age: 52.2 y |
||
| Torlontano 1999 [48] Case-control study |
N = 32 women N1 = 8 with SH F/M = 8/0 Mean age: 54.0 ± 18.4 y (26–75 y) |
N2 = 24 without SH F/M = 24/0 Mean age: 57.3 ± 10.0 y (38–76 y) |
N3 = 64 controls F/M = 64/0 Mean age: 56.4 ± 12.3 y (22–76 y) |
|
| Osella 2001 [49] Case-control study |
N = 27 N1 = 27 with AI F/M = 18/9 Median age: 57 y (42–73 y) of these N2 = 8 with SCS F/M = 5/3 Median age: 55.87 y |
N3 = 54 controls F/M = 36/18 Median age: 56.5 y (41–73 y) |
||
| Chiodini 2001 [50] Longitudinal study |
N = 24 N1 = 7 with SH F/M = 7/0 Mean age: 42.4 ± 16.7 y (26–72 y) |
N2 = 17 without SH F/M = 17/0 Mean age: 56.0 ± 11.8 y (38–77 y) |
||
| Tauchmanova 2001 [51] Case-control study |
N = 34 N1 =15 with overt CS F/M = 9/6 Mean age: 41.73 ± 10.2 y (21–50 y) |
N2 = 19 with SCS
F/M = 11/8 Mean age: 44.5 ± 9.8 y (25–59 y) |
N3 = 76 controls F/M = 46/30 Mean age: 46.5 ± 13.7 y |
|
| Chiodini 2002 [52] Cross-sectional study |
N = 38 N1 = 13 with SH F/M = 0/13 Mean age: 61.4 ± 11.3 y (40–75 y) |
N2 = 25 without SH F/M = 0/25 Mean age: 55.2 ± 12.6 y (21–78 y) |
N3 = 38 controls Mean age: 56.9 ± 11.8 y (26–74 y) |
|
| Francucci 2002 [53] Case-control study |
N = 38 women N1 = 15 with CS F/M = 15/0 Mean age: 46.5 ± 14.8 y |
N2 = 23 with AI
F/M = 23/0 Mean age: 57.6 ± 10.9 y |
N3 = 20 controls F/M = 20/0 Mean age: 51.5 ± 9 y |
|
| Hadjidakis 2003 [54] Cross-sectional study |
N = 42 N1 = 18 with SH F/M = 24/0 Mean age: 59.1 ± 6.3 y (48–74 y) |
N2 = 24 without SH F/M = 18/0 Mean age: 63.6 ± 5.1 y (53–72 y) |
||
| Chiodini 2004 [55] Case-control study |
N = 70 women Premenopausal women: N1 = 7 with SH F/M = 7/0 Mean age: 42.9 ± 3.5 y (26–50 y) N2 = 14 without SH F/M = 14/0 Mean age: 39.3 ± 2.2 y (24–52 y) |
N3 = 23 controls F/M = 23/0 Mean age: 41.7 ± 2.0 y (21–54 y) N3 = 61 controls F/M = 61/0 Mean age: 60.8 ± 0.9 y (44–75 y) |
Postmenopausal women: N1 = 14 with SH F/M = 14/0 Mean age: 63.9 ± 2.2 y (46–79 y) |
N2 = 35 without SH F/M = 35/0 Mean age: 61.5 ± 1.4 y (48–80 y) |
| Tauchmanova 2007 [56] Case-control study |
N = 71 women N1 = 36 with overt CS F/M = 36/0 Median age: 42 y (28–66 y) |
N2 = 35 with SCS
F/M = 35/0 Median age: 46 y (30–68 y) |
N3 = 71 controls Median age: 44 y (28–68 y) |
|
| Tauchmanova 2009 [57] Case-control study |
N = 46 N1 = 23 with SCS treated with clodronate F/M = 23/0 Mean age: 42.4 ± 6.4 y |
N2 = 23 with SCS (untreated)
F/M = 23/0 Mean age: 43.5 ± 6.1 y |
||
| Chiodini 2009 [58] Retrospective study |
N = 287 N1 = 85 with SH F/M = 53/32 Mean age: 62.9 ± 9.9 y (34–79 y) |
N2 = 202 without SH F/M = 123/79 Mean age: 61.2 ± 11.4 y (21–81 y) |
N3 = 194 controls F/M = 104/90 Mean age: 61.1 ± 13.7 y (21–79 y) |
|
| Chiodini 2009 [59] Case-control study |
N = 88 men N1 = 22 with SH F/M = 0/22 Mean age: 65.8 ± 10.7 y (42–86 y) |
N2 = 66 without SH F/M = 0/66 Mean age: 60.9 ± 12.9 y (21–83 y) |
N3 = 90 controls F/M = 0/90 Mean age: 61.8 ± 14.2 (23–90 y) |
|
| Toniato 2009 [60] Prospective study |
N = 45 N1 = 23 with adrenalectomy: F/M = 11/12 Mean age: 63 ± 4.1 y |
N2 = 22 with conservative management: F/M = 12/10 Mean age: 64 ± 1.8 y |
||
| Morelli 2010 [61] Retrospective study |
N = 231 with AI
F/M = 120/111 Mean age: 62.9 ± 10.1 y |
|||
| Morelli 2011 [62] Cross-sectional study |
N = 103 female At baseline: N1 = 27 with SH F/M = 27/0 Mean age: 65.0 ± 8.7 y (41–83 y) N2 = 76 without SH F/M = 76/0 Mean age: 62.7 ± 10.3 y (28–80 y) |
After 24 months of follow-up: N1 = 27 with SH F/M = 27/0 Mean age: 67.0 ± 8.5 y (43–85 y) N2 = 76 without SH F/M = 76/0 Mean age: 64.9 ± 10.2 y (30–82 y) |
||
| Eller-Vainicher 2012 [63] Case-control study |
N = 102 N1 = 34 with SH F/M = 19/15 Mean age: 66.3 ± 8.3 y (45–79 y) |
N2 = 68 without SH F/M = 44/24 Mean age: 67.5 ± 8.7 y (47–83 y) |
N3 = 70 controls F/M = 48/22 Mean age: 67.7 ± 14.4 y (37–85 y) |
|
| Iacobone 2012 [64] Prospective study |
N = 35 N1 = 22 with adrenalectomy: F/M = 8/12 Median: 55 y (36–78 y) |
N2 = 15 with conservative management: F/M = 7/8 Median: 58 y (39–75 y) |
||
| Morelli 2013 [65] Prospective study |
N = 213 BAI: N1 = 10 with SH F/M = 4/6 Mean age: 65.6 ± 5.3 y (57–74 y) |
N2 = 28 without SH F/M = 20/8 Mean age: 63.7 ± 9.9 y (41–82 y) |
UAI:
N1 = 41 with SH F/M = 28/13 Mean age: 62.1 ± 11.6 y (39–83 y) |
N2 = 134 without SH F/M = 88/46 Mean age: 63.7 ± 11.0 y (31–85 y) |
| Palmieri 2013 [66] Cross-sectional, prospective study |
N = 70 N1 = 16 with SH F/M = 7/9 Mean age: 62.5 ± 10.6 y (34–77 y) |
N2 = 54 without SH F/M = 34/20 Mean age: 61.5 ± 10.3 y (39–77 y) |
||
| Lasco 2014 [67] Cross-sectional study |
N = 50 women N1 = 3 with SH Median age: 57 ± 3 y |
N2 = 47 without SH Median age: 58 ± 4 y |
||
| Perogamvros 2015 [68] Retrospective study |
N = 33 N1 = 14 with adrenalectomy: F/M = 14/0 Mean age: 54.9 ± 6.7 y |
N2 = 19 with conservative management: F/M = 14/5 Mean age: 59 ± 8.7 y |
||
| Morelli 2016 [69] Retrospective (cross-sectional arm) and prospective (longitudinal arm) |
N = 444, of these 126 with AI N1 = 96 patients without incident VFx F/M = 64/32 Mean age: 62.9 ± 9.5 y (27–80 y) |
N2 = 30 patients with incident VFx
F/M = 16/14 Mean age: 65.5 ± 9.2 y (41–83 y) |
||
| Salcuni 2016 [70] Cross-sectional and prospective interventional study |
N = 55 Surgical intervention: N1 = 32 Baseline: F/M = 22/10 Mean age: 61.3 ± 8.1 y (38–75 y) End of follow-up Mean age: 64.7 ± 8.7 y (40–79 y) |
Conservative management: N2 = 23 Baseline: F/M = 10/13 Mean age: 65.4 ± 7.05 y (51–75 y) End of follow-up: Mean age: 67.7 ± 6.9 y (53–78 y) |
||
| Ognjanovic 2016 [71] Cross-sectional study |
N = 152 UAI: N1 = 105 F/M = 68/37 Mean age: 58.0 ± 11.1 y |
BAI: N2 = 47
F/M = 38/9 Mean age: 59.2 ± 10.2 y |
||
| Vinolas 2018 [72] Cross-sectional study |
N = 110 N1 = 53 with CS F/M = 42/11 Mean age: 49.9 ± 12.8 y |
N2 = 39 with MACS
F/M = 34/5 Mean age: 57.8 ± 9.3 y |
N3 = 18 with NFAI
F/M = 13/5 Mean age: 59.2 ± 9.1 y |
|
| Kim 2018 [73] Cross-sectional study |
N = 435 Men (N = 247): N1 = 4 adrenal CS Mean age: 47.5 ± 6.6 y N2 = 30 with SH Mean age: 59.5 ± 8.4 y N3 = 213 with NFAI Mean age: 54.5 ± 9.8 y |
Women (N = 188): N1 = 15 adrenal CS Mean age: 41.9 ± 9.7 y N2 = 31 with SH Mean age: 51.2 ± 13.3 y N3 = 142 with NFAI Mean age: 55.4 ± 10.8 y |
||
| Ahn 2019 [74] Cross-sectional study |
N = 795 Premenopausal women (N = 77): N1 = 18 with SH Mean age: 38.6 ± 6.1 y N2 = 59 NFAI Mean age: 42.5 ± 6.2 y |
Postmenopausal women (N = 237): N1 = 38 with SH Mean age: 59.7 ± 7.4 y N2 = 199 NFAI Mean age: 59.4 ± 7.4 y |
Men (N = 481): N1 = 53 with SH Mean age: 56.9 ± 9.7 y N2 = 428 NFAI Mean age: 55.3 ± 9.6 y |
|
| Moraes 2020 [75] Cross-sectional study |
N = 75 N1 = 30 ACS F/M = 26/4 Median age: 60 y (42–77 y) |
N2 = 45 NFAI
F/M = 32/13 Median age: 59 y (32–76 y) |
||
| Athimulam 2020 [76] Cross-sectional study |
N = 213
N1 = 22 with CS F/M = 18/4 Mean age: 41.5 y (18–61 y) |
N2 = 92 with MACS
F/M = 57/35 Mean age: 59.5 y (28–82 y) |
N3 = 99 with NFAI
F/M = 67/32 Mean age: 59 y (28–93 y) |
|
| Ueland 2020 [77] Retrospective study |
N = 165 N1 = 83 with ACS F/M = 58/25 Median age: 65 y (29–86 y) |
N2 = 82 with NFAI
F/M = 48/34 Median age: 68.5 y (33–82 y) |
||
| Ishida 2021 [78] Retrospective study |
N = 67 N1 = 55 with ACS F/M = 33/23 Mean age: 61.5 ± 10.1 y |
N2 = 12 with NFAI
F/M = 5/7 Mean age: 66.0 ± 8.9 y |
||
| Podbregar 2021 [79] Prospective study |
N = 67 with NFAI
F/M = 47/20 Mean age: 57.9 y |
|||
| Li 2021 [80] Cohort study |
N1 = 1004 with AI
F/M = 582/422 Mean age: 62.8 y (20.5–96.4 y) |
N2 = 1004 controls F/M = 582/422 Mean age: 62.7 y (20.5–95.5 y) |
||
| Yano 2022 [81] Cross-sectional study |
N = 194 N1= 97 with ACS F/M = 60/37 Median age: 62.0 y |
N2 = 97 with NFAI
F/M = 52/45 Median age: 58.0 y |
||
| Izawa 2022 [82] Cross-sectional observational study |
N = 237 with adrenal adenoma associated with cortisol excess N1 = 112 with osteoporosis/osteopenia F/M = 99/13 Median age: 57 y (42–64 y) |
N2= 125 without osteoporosis/osteopenia F/M = 83/42 Median age: 55 y (46–63 y) |
||
Abbreviations: ACS = autonomous cortisol secretion; AI = adrenal incidentaloma; ACTH = adrenocorticotropic hormone; BAI = bilateral adrenal incidentaloma; CRH = corticotropin-releasing hormone; DST = dexamethasone suppression test; LDDST = low dose dexamethasone suppression test; F = female; HPA = hypothalamic–pituitary–adrenal; N = number of patients; NFAI = non-functioning adrenal incidentaloma; M = male; MACS = mild autonomous cortisol secretion; SCS = subclinical Cushing syndrome; SH = subclinical hypercortisolism; UFC = urinary free cortisol; UAI = unilateral AI; VFx = vertebral fractures; y = year; (red = SCS or SH subgroups; blue = AI or NFAI subgroup); green colour means CS; blue colour means AI/NFAI; red colour means ACS, MACS, SCS or preclinical SCS.