Table 1.
Demographic Data, Clinical Characteristics and Catecholamine Metabolomic Profiles in Patients with and without Metastatic PPGLs
| Reference Population | Patient Population | ||||
|---|---|---|---|---|---|
| |
|
|
|||
| Demographic/Clinical Data | No tumor | No Metastases | Metastases | P value* | |
| N | 846 | 260 | 105 | ||
| Age (Mean±SD) | 41±14 | 41±17 | 37±17 | 0.0399 | |
| Gender (M/F) | 467 / 379 | 129 / 131 | 60 / 45 | 0.2047 | |
| Tumor location (A/E/B)† | no tumors | 223/28/9 | 34/65/6 | 0.0001 | |
| Tumor Volume (Mean±SE)‡ | no tumors | 54±6 | 195±26 | 0.0001 | |
| SDHB mutation (yes/no)§ | not tested | 7 / 253 | 41 / 64 | 0.0001 | |
| Norepinephrine & metabolites | Mean Ref. Intervals | Mean 95% CI | Mean 95% CI | P value* | AUC |
|---|---|---|---|---|---|
| Plasma NE (nmol/L) | 1.46 [0.51-4.18] | 5.57 (4.91-6.35) | 10.02 (7.75-12.94) | 0.0001 | 0.630 |
| Plasma f-NMN (nmol/L) | 0.29 [0.11-0.74] | 3.52 (3.05-4.07) | 5.51 (4.10-7.40) | 0.0031 | 0.603 |
| Plasma d-NMN (nmol/L) | 10.54 [3.85-28.12] | 78.3 (65.3-93.98) | 145.8 (99.4-213.9) | 0.0037 | 0.656 |
| Plasma DHPG (nmol/L) | 4.88 [2.69-8.88] | 7.86 (7.35-8.41) | 9.20 (8.16-10.36) | 0.0174 | 0.582 |
| Urine NE (μmol/day) | 0.22 [0.08-0.61] | 0.99 (0.84-1.16) | 1.48 (1.13-1.93) | 0.0094 | 0.587 |
| Urine d-NMN (umol/day) | 1.37 [0.45-4.14] | 9.02 (7.63-10.68) | 14.92 (11.01-20.21) | 0.0023 | 0.613 |
| Urine VMA (μmol/day) | 17.61 [7.06-43.39] | 48.95 (43.08-55.62) | 69.68 (56.15-86.47) | 0.0054 | 0.616 |
| Epinephrine & metabolites | Mean Ref. Intervals | Mean 95% CI | Mean 95% CI | P value* | AUC |
|---|---|---|---|---|---|
| Plasma EPI (nmol/L) | 0.09 [0.01-0.67] | 0.30 (0.25-0.36) | 0.17 (0.13-0.22) | 0.0012 | 0.626 |
| Plasma f-MN (nmol/L) | 0.13 [0.04-0.45] | 0.66 (0.54-0.81) | 0.24 (0.18-0.33) | 0.0001 | 0.683 |
| Plasma d-MN (nmol/L) | 3.91 [1.00-14.90] | 21.05 (16.20-27.36) | 10.8 (6.70-17.31) | 0.0232 | 0.624 |
| Urine EPI (μmol/day) | 0.02 [0.01-0.09] | 0.07 (0.06-0.9) | 0.03 (0.02-0.04) | 0.0001 | 0.663 |
| Urine d-MN (μmol/day) | 0.39 [0.09-1.56] | 2.19 (1.69-2.85) | 0.92 (0.66-1.28) | 0.0001 | 0.661 |
| Dopamine, DOPA & metabolites | Mean Ref. Intervals | Mean 95% CI | Mean 95% CI | P value* | AUC |
|---|---|---|---|---|---|
| Plasma DA (nmol/L) | 0.05 [0.01-0.41] | 0.13 (0.11-0.15) | 0.40 (0.25-0.62) | 0.0001 | 0.630 |
| Plasma f-MTY (nmol/L) | 0.02 [0.00-0.11] | 0.07 (0.06-0.08) | 0.33 (0.22-0.50) | 0.0001 | 0.739 |
| Plasma d-MTY (nmol/L) | 1.22 [0.20-7.41] | 3.79 (3.10-4.63) | 7.91 (3.70-16.92) | 0.0097 | 0.591 |
| Plasma DOPAC (nmol/L) | 7.92 [3.78-16.59] | 8.95 (8.35-9.59) | 10.59 (8.96-12.52) | 0.0313 | 0.564 |
| Plasma DOPA (nmol/L) | 7.94 [4.98-12.63] | 9.51 (8.94-10.11) | 11.69 (10.16-13.46) | 0.0023 | 0.549 |
| Urine DA (μmol/day) | 1.19 [0.39-3.66] | 1.70 (1.57-1.84) | 2.41 (1.97-2.95) | 0.0006 | 0.592 |
Denotes significance of difference between groups with and without metastases
Tumor location indicates adrenal (A), extra-adrenal (E) or both adrenal and extra-adrenal (B) primary tumors
Tumor size indicates the volume (cubic cm) of the primary tumor or sets of multifocal primary tumors first diagnosed
Numbers of patients with no SDHB mutations detected include 100 who were not tested and in who SDHB mutations remain possible (80 without metastases and 20 with metastases who were excluded from subsequent comparisons of patients with and with SDHB mutations).
Catecholamine metabolomic data are shown as geometric means with reference intervals (Ref.Intervals) determined from the 2.5 and 97.5 percentiles of the reference population and the 95% confidence intervals of the mean (95% CI) shown for the two PPGL patient groups. All 18 analytes were higher (P<0.007) in both groups of PPGL patients compared to the reference group.
Abbreviations: AUC, area under ROC curves; NE; norepinephrine; f-NMN, free normetanephrine; d-NMN, deconjugated normetanephrine; DHPG, 3,4-dihydroxyphenylglycol; VMA, vanillylmandelic acid; EPI, epinephrine; f-MN, free metanephrine; d-MN, deconjugated metanephrine; DA, dopamine; f-MTY, free methoxytyramine; d-MTY, deconjugated methoxytyramine; DOPAC; 3-4-dihydroxyphenylacetic acid; DOPA, 3,4-dihydroxyphenylalanine.