Table 1.
Baseline characteristics of all patients (n=81) and by clinical criteria of cortisol excess severity.
| Subgroup Analysis | ||||||||
|---|---|---|---|---|---|---|---|---|
| n=81 | MACE 30(37.0%) |
Moderate CS 24 (29.7%) |
Severe CS 27 (33.3%) |
P | MACE vs Mod CS | MACE vs Sev CS | Mod vs Sev CS | |
| A. Demographic characteristics | ||||||||
| Sex: female | 64 (79.0%) | 20 (66.7%) | 19 (79.2%) | 25 (92.6%) | 0.05 | 0.30 | 0.02 | 0.16 |
| Race: Caucasian | 80 (98.8%) | 29 (96.7%) | 24 (100%) | 27 (100%) | 0.42 | 0.36 | 0.34 | - |
| BMI, kg/m2 | 31.1 (27.3–37.7) | 28.5 (25.4–32.7) | 33.5 (29.5–39.2) | 32.3 (27.4–40.5) | 0.02 | 0.007 | 0.06 | 0.60 |
| Tobacco use: present | 31 (38.3%) | 7 (23.3%) | 13 (51.2%) | 11 (40.7%) | 0.07 | 0.02 | 0.16 | 0.34 |
| Age at the time of tumor diagnosis, years | 52 (42–62) | 60 (49–67) | 51 (44–61) | 45 (31–56) | 0.0007 | 0.06 | 0.0003 | 0.03 |
| Duration of symptoms, months | 11 (0–21) | 0 (0–8) | 6 (0–12) | 24 (12–24) | <0.0001 | 0.02 | <0.0001 | 0.002 |
| Mode of discovery: incidental | 54 (66.7%) | 25 (83.3%) | 20(83.3%) | 9 (33.3%) | <0.0001 | 1.00 | 0.0001 | 0.0003 |
| B. Tumor Characteristics and therapy | ||||||||
| Size of resected tumor, mm | 39 (30.0–48) | 40 (30–48) | 41 (33–48) | 34 (28–42) | 0.15 | 0.65 | 0.15 | 0.07 |
| Pathology: adenoma | 76 (93.8%) | 28 (93.3%) | 23 (95.8%) | 25 (92.6%) | 0.88 | 0.69 | 0.91 | 0.62 |
| C. Clinical characteristics | ||||||||
| Hypertension | 62 (76.5%) | 21 (70.0%) | 20 (83.3%) | 21 (77.8%) | 0.51 | 0.25 | 0.50 | 0.62 |
| Weight gain | 51 (63.0%) | 98 (26.7%) | 17 (70.8%) | 26 (96.3%) | <0.0001 | 0.001 | <0.0001 | 0.01 |
| Dyslipidemia | 49 (60.5%) | 17 (56.7%) | 19 (79.2%) | 13 (48.1%) | 0.07 | 0.08 | 0.52 | 0.02 |
| Abnormal Glucose metabolism a | 45 (55.6%) | 13 (43.3%) | 15 (62.5%) | 17 (63.0%) | 0.24 | 0.16 | 0.14 | 0.97 |
| Low bone density b | 30 (37.0%) | 10 (33.3%) | 9 (37.5%) | 11 (40.7%) | 0.84 | 0.75 | 0.56 | 0.81 |
| Cerebrovascular disease | 5 (6.1%) | 0 (0%) | 4 (16.7%) | 1 (3.7%) | 0.03 | 0.02 | 0.29 | 0.12 |
| D. Physical exam findings | ||||||||
| Supraclavicular or dorsocervical fat pads | 34 (42.0%) | 0 (0.0%) | 7 (29.2%) | 27 (100.0%) | <0.0001 | 0.001 | <0.0001 | <0.0001 |
| Central obesity | 32 (39.5%) | 0 (0.0%) | 7 (29.2%) | 25 (92.6%) | <0.0001 | 0.001 | <0.0001 | <0.0001 |
| Rounding of the face | 31 (38.3%) | 0 (0.0%) | 5 (20.83%) | 26 (96.3%) | <0.0001 | 0.009 | <0.0001 | <0.0001 |
| Muscle weakness | 19 (23.5%) | 0 (0.0%) | 5 (20.83%) | 14 (51.2%) | <0.0001 | 0.009 | <0.0001 | 0.02 |
| Skin Changes (thinning, easy bruising, striae) | 19 (23.5%) | 0 (0.0%) | 2 (8.3%) | 17 (63.0%) | <0.0001 | 0.11 | <0.0001 | <0.0001 |
| E. Laboratory results | ||||||||
| Number of abnormal HPA axis tests | 3 (2–4) | 2 (1–3) | 3 (2–4) | 3 (4–5) | <0.0001 | 0.07 | <0.0001 | 0.0003 |
| Urine free cortisol, μg/24h, nmol/24h, n=71 (Reference range: 3.5–45 μg/24h, 10–124 nmol/24h) |
41 (19–118) 113 (52–326) |
26.0 (17.0–44.0) 72 (47–121) |
40.0 (13.0–73.0) 110 (36–201) |
104.0 (41.0–254.0) 287 (113–701) |
<0.0001 | 0.50 | <0.0001 | 0.001 |
| Post 1-mg DST serum cortisol, μg/dL, nmol/L, n=69 (Reference range: <1.8 μg/dL, <50 nmol/L) |
5.5 (2.9–11.0) 152 (80–304) |
5.6 (3.0–9.1) 155 (81–251) |
4.6 (2.7–8.2) 127 (75–226) |
9.0 (2.8–16.8) 247 (78–462) |
0.24 | 0.59 | 0.17 | 0.14 |
| ACTH, pg/mL, pmol/L, n=71 (Reference range: 10–60 pg/dL, 2.2–13.2 pmol/L, AM draw) |
5 (5–7.5) 1.1 (1.1–1.7) |
6.6 (5–12) 1.5 (1.1–2.6) |
5 (5–7.3) 1.1 (1.1–1.6) |
5 (5–5.8) 1.1 (1.1–1.3) |
0.01 | 0.05 | 0.003 | 0.46 |
| 8AM serum cortisol, μg/dL, nmol/L, n=61 (Reference range 7–25 μg/dL, 193–690 nmol/L) |
14 (9.9–20) 386 (273–552) |
11 (9.8–18) 304 (270–497) |
13 (8.8–19.8) 359 (242–545) |
17 (14.0–21.2) 469 (386–585) |
0.05 | 0.69 | 0.02 | 0.11 |
| Afternoon serum cortisol, μg/dL, nmol/L, n=48 (Reference range 2–14 μg/dL) |
14.0 (9.4–20.0) 386 (261–552) |
9.6 (8.1–16) 265 (224–442) |
12.5 (9.3–16.5) 345 (255–457) |
17.5 (11.5–22.8) 483 (317–628) |
0.10 | 0.57 | 0.07 | 0.13 |
| Midnight salivary cortisol, ng/dL, nmol/dL, n=21 (Reference range <100 ng/dL, <2.8 nmol/dL) |
133 (56–548) 3.7 (1.5–15.1) |
56 (50–72.5) 1.5 (1.4–2.0) |
60.5 (50–117.5) 1.7 (1.4–3.2) |
382 (137.5–742) 10.5 (3.8–20.5) |
0.009 | 0.88 | 0.01 | 0.03 |
| Loss of circadian rhythm c, n=44 | 36/44 (81.8%) | 8/12 (66.7%) | 6/10 (60.0%) | 22/22 (100%) | 0.006 | 0.75 | 0.004 | 0.001 |
| DHEA-S, μg/dL, μmol/L, n=52 (Reference range: 44–332 μg/dL, 1.2–9.0 μmol/L) |
30.2 (15–55.1) 0.8 (0.4–1.5) |
29.3 (15–81.9) 0.8 (0.4–2.2) |
38.3 (27.4–56.3) 1.0 (0.7–1.5) |
22.1 (15–48.0) 0.6 (0.4–1.3) |
0.46 | 0.70 | 0.49 | 0.21 |
Continuous data are summarized as median and interquartile ranges. Categorical data are presented as frequencies and percentages. All P-values <0.05 were considered significant.
a
Abnormal glucose metabolism: diabetes mellitus or pre-diabetes mellitus;
b
Low bone density: osteopenia or osteoporosis;
c
Loss of circadian rhythm defined as changes in normal variability of cortisol throughout the day (i.e. elevated PM serum cortisol)
Abbreviations used: ACTH, corticotropin; BMI, body mass index; CS, Cushing syndrome; DHEA-S: Dehydroepiandrosterone sulfate; DST, dexamethasone suppression test; HPA, hypothalamic-pituitary-adrenal; and, MACE, mild autonomous cortisol excess.