Table 2. Associated Diagnoses and Symptoms in Patients in High-risk Group 1 and Patients in High-risk Group 2 Compared With Matched Controls.
| Time and diagnosis | Patients, No. (%) after matching | OR (95% CI) | P valueb | Patients, No. (%) after matching | OR (95% CI) | P valueb | ||
|---|---|---|---|---|---|---|---|---|
| High-risk group 1 (n = 20 175)a | Matched controls (n = 20 175) | High-risk group 2 (n = 24 905)c | Matched controls (n = 24 905) | |||||
| 0 to ≤1 y | ||||||||
| Osteopenia or osteoporosis | 2662 (13.2) | 1099 (5.4) | 2.64 (2.45-2.84) | <.001 | 1423 (5.7) | 1065 (4.3) | 1.36 (1.25-1.47) | <.001 |
| Fractures | 719 (3.6) | 478 (2.4) | 1.52 (1.35-1.71) | <.001 | 691 (2.8) | 603 (2.4) | 1.15 (1.03-1.29) | .01 |
| Urolithiasis | 771 (3.8) | 281 (1.4) | 2.81 (2.45-3.23) | <.001 | 746 (3.0) | 378 (1.5) | 2.00 (1.77-2.27) | <.001 |
| MDD | 2009 (10.0) | 1393 (6.9) | 1.49 (1.39-1.60) | <.001 | 2507 (10.1) | 1565 (6.3) | 1.67 (1.56-1.78) | <.001 |
| Anxiety disorders | 1920 (9.5) | 1347 (6.7) | 1.47 (1.37-1.58) | <.001 | 2481 (10.0) | 1689 (6.8) | 1.52 (1.43-1.62) | <.001 |
| HTN | 9107 (45.1) | 6231 (30.9) | 1.84 (1.77-1.92) | <.001 | 8872 (35.6) | 5795 (23.3) | 1.83 (1.76-1.90) | <.001 |
| GERD | 2952 (14.6) | 2047 (10.1) | 1.52 (1.43-1.61) | <.001 | 3186 (12.8) | 2241 (9.0) | 1.48 (1.40-1.57) | <.001 |
| Malaise or fatigue | 2065 (10.2) | 1328 (6.6) | 1.62 (1.51-1.74) | <.001 | 2086 (8.4) | 1455 (5.8) | 1.47 (1.38-1.58) | <.001 |
| Joint pain or myalgias | 3461 (17.2) | 2385 (11.8) | 1.55 (1.46-1.63) | <.001 | 3745 (15.0) | 2834 (11.4) | 1.38 (1.31-1.45) | <.001 |
| Constipation | 1247 (6.2) | 719 (3.6) | 1.78 (1.54-1.96) | <.001 | 1334 (5.4) | 687 (2.8) | 2.00 (1.82-2.19) | <.001 |
| Insomnia | 885 (4.4) | 524 (2.6) | 1.72 (1.54-1.92) | <.001 | 937 (3.8) | 570 (2.3) | 1.67 (1.50-1.86) | <.001 |
| Polyuria | 874 (4.3) | 506 (2.5) | 1.76 (1.58-1.97) | <.001 | 905 (3.6) | 607 (2.4) | 1.51 (1.36-1.68) | <.001 |
| Weakness | 1374 (6.8) | 872 (4.3) | 1.62 (1.48-1.77) | <.001 | 1413 (5.7) | 891 (3.6) | 1.62 (1.49-1.77) | <.001 |
| Abdominal pain | 2142 (10.6) | 1573 (7.8) | 1.41 (1.31-1.50) | <.001 | 3067 (12.3) | 1916 (7.7) | 1.69 (1.59-1.79) | <.001 |
| Headache | 1104 (5.5) | 794 (3.9) | 1.41 (1.29-1.55) | <.001 | 1320 (5.3) | 891 (3.6) | 1.51 (1.38-1.65) | <.001 |
| Nausea | 814 (4.0) | 498 (2.5) | 1.66 (1.48-1.86) | <.001 | 1013 (4.1) | 567 (2.3) | 1.82 (1.64-2.02) | <.001 |
| Amnesia | 738 (3.7) | 506 (2.5) | 1.48 (1.32-1.66) | <.001 | 992 (4.0) | 566 (2.3) | 1.78 (1.61-1.98) | <.001 |
| Gallstones | 373 (1.8) | 217 (1.1) | 1.73 (1.46-2.05) | <.001 | 480 (1.9) | 282 (1.1) | 1.72 (1.48-1.98) | <.001 |
| 366 d to ≤2 y | ||||||||
| Osteopenia or osteoporosis | 2718 (13.5) | 1070 (5.3) | 2.78 (2.58-2.99) | <.001 | 1461 (5.9) | 1002 (4.0) | 1.49 (1.37-1.61) | <.001 |
| Fractures | 647 (3.2) | 367 (1.8) | 1.79 (1.57-2.04) | <.001 | 581 (2.3) | 370 (1.5) | 1.58 (1.39-1.81) | <.001 |
| Urolithiasis | 651 (3.2) | 198 (1.0) | 3.36 (2.87-3.95) | <.001 | 539 (2.2) | 225 (0.9) | 2.43 (2.08-2.84) | <.001 |
| MDD | 1909 (9.5) | 1164 (5.8) | 1.71 (1.58-1.84) | <.001 | 2088 (8.4) | 1213 (4.9) | 1.79 (1.66-1.92) | <.001 |
| Anxiety disorders | 1740 (8.6) | 1105 (5.5) | 1.63 (1.51-1.76) | <.001 | 2056 (8.3) | 1379 (5.5) | 1.54 (1.43-1.65) | <.001 |
| HTN | 8940 (44.3) | 5057 (25.1) | 2.38 (2.28-2.48) | <.001 | 7814 (31.4) | 4327 (17.4) | 2.17 (2.08-2.27) | <.001 |
| GERD | 2690 (13.3) | 1606 (8.0) | 1.78 (1.67-1.90) | <.001 | 2676 (10.7) | 1643 (6.6) | 1.70 (1.60-1.82) | <.001 |
| Malaise or fatigue | 1531 (7.6) | 898 (4.5) | 1.76 (1.62-1.92) | <.001 | 1487 (6.0) | 958 (3.8) | 1.59 (1.46-1.73) | <.001 |
| Joint pain or myalgias | 3327 (16.5) | 2004 (9.9) | 1.79 (1.69-1.90) | <.001 | 3167 (12.7) | 2285 (9.2) | 1.44 (1.36-1.53) | <.001 |
| Constipation | 1001 (5.0) | 472 (2.3) | 2.18 (1.95-2.44) | <.001 | 935 (3.8) | 443 (1.8) | 2.15 (1.92-2.42) | <.001 |
| Insomnia | 725 (3.6) | 395 (2.0) | 1.86 (1.65-2.11) | <.001 | 754 (3.0) | 418 (1.7) | 1.83 (1.62-2.06) | <.001 |
| Polyuria | 786 (3.9) | 420 (2.1) | 1.91 (1.69-2.15) | <.001 | 724 (2.9) | 515 (2.1) | 1.42 (1.27-1.59) | <.001 |
| Weakness | 948 (4.7) | 547 (2.8) | 1.77 (1.59-1.97) | <.001 | 949 (3.8) | 548 (2.2) | 1.76 (1.58-1.96) | <.001 |
| Abdominal pain | 1698 (8.4) | 949 (4.7) | 1.86 (1.72-2.02) | <.001 | 2020 (8.1) | 1102 (4.4) | 1.91 (1.77-2.06) | <.001 |
| Headache | 923 (4.6) | 505 (2.5) | 1.87 (1.67-2.09) | <.001 | 890 (3.6) | 543 (2.2) | 1.66 (1.49-1.85) | <.001 |
| Nausea | 598 (3.0) | 292 (1.4) | 2.08 (1.81-2.40) | <.001 | 614 (2.5) | 277 (1.1) | 2.25 (1.95-2.59) | <.001 |
| Amnesia | 635 (3.1) | 373 (1.8) | 1.73 (1.52-1.96) | <.001 | 683 (2.7) | 336 (1.3) | 2.06 (1.81-2.35) | <.001 |
| Gallstones | 265 (1.3) | 124 (0.6) | 2.15 (1.74-2.67) | <.001 | 264 (1.1) | 107 (0.4) | 2.48 (1.98-3.11) | <.001 |
| 731 d to ≤3 y | ||||||||
| Osteopenia or osteoporosis | 2945 (14.6) | 1254 (6.2) | 2.58 (2.41-2.76) | <.001 | 1635 (6.6) | 1117 (4.5) | 1.50 (1.38-1.62) | <.001 |
| Fractures | 679 (3.4) | 418 (2.1) | 1.65 (1.46-1.86) | <.001 | 616 (2.5) | 424 (1.7) | 1.46 (1.29-1.66) | <.001 |
| Urolithiasis | 644 (3.2) | 175 (0.9) | 3.77 (3.19-4.46) | <.001 | 549 (2.2) | 230 (0.9) | 2.42 (2.07-2.82) | <.001 |
| MDD | 2024 (10.0) | 1200 (5.9) | 1.76 (1.64-1.90) | <.001 | 2087 (8.4) | 1247 (5.0) | 1.74 (1.61-1.87) | <.001 |
| Anxiety disorders | 1835 (9.1) | 1163 (5.8) | 1.64 (1.52-1.77) | <.001 | 2175 (8.7) | 1433 (5.8) | 1.57 (1.46-1.68) | <.001 |
| HTN | 9124 (45.2) | 5346 (26.5) | 2.29 (2.20-2.39) | <.001 | 8121 (32.6) | 4670 (18.8) | 2.10 (2.01-2.19) | <.001 |
| GERD | 2800 (13.9) | 1760 (8.7) | 1.69 (1.58-1.80) | <.001 | 2801 (11.2) | 1803 (7.2) | 1.62 (1.53-1.73) | <.001 |
| Malaise or fatigue | 1574 (7.8) | 917 (4.5) | 1.78 (1.63-1.93) | <.001 | 1488 (6.0) | 1028 (4.1) | 1.48 (1.36-1.60) | <.001 |
| Joint pain or myalgias | 3285 (16.3) | 2082 (10.3) | 1.69 (1.59-1.79) | <.001 | 3246 (13.0) | 2361 (9.5) | 1.43 (1.35-1.51) | <.001 |
| Constipation | 1017 (5.0) | 511 (2.5) | 2.04 (1.83-2.28) | <.001 | 948 (3.8) | 513 (2.1) | 1.88 (1.69-2.10) | <.001 |
| Insomnia | 774 (3.8) | 436 (2.2) | 1.81 (1.60-2.03) | <.001 | 765 (3.1) | 484 (1.9) | 1.60 (1.43-1.79) | <.001 |
| Polyuria | 849 (4.2) | 511 (2.5) | 1.69 (1.51-1.89) | <.001 | 737 (3.0) | 525 (2.1) | 1.42 (1.26-1.59) | <.001 |
| Weakness | 1034 (5.1) | 577 (2.9) | 1.84 (1.65-2.04) | <.001 | 914 (3.7) | 587 (2.4) | 1.58 (1.42-1.75) | <.001 |
| Abdominal pain | 1725 (8.6) | 1041 (5.2) | 1.72 (1.59-1.86) | <.001 | 2056 (8.3) | 1145 (4.6) | 1.87 (1.73-2.01) | <.001 |
| Headache | 848 (4.2) | 480 (2.4) | 1.80 (1.61-2.02) | <.001 | 892 (3.6) | 542 (2.2) | 1.67 (1.50-1.86) | <.001 |
| Nausea | 576 (2.9) | 289 (1.3) | 2.02 (1.75-2.33) | <.001 | 575 (2.3) | 303 (1.2) | 1.92 (1.67-2.21) | <.001 |
| Amnesia | 681 (3.4) | 404 (2.0) | 1.71 (1.51-1.94) | <.001 | 737 (3.0) | 379 (1.5) | 1.97 (1.74-2.24) | <.001 |
| Gallstones | 267 (1.3) | 132 (0.7) | 2.04 (1.65-2.51) | <.001 | 296 (1.2) | 144 (0.6) | 2.07 (1.69-2.53) | <.001 |
| Entire study period (0-3 y) | ||||||||
| Osteopenia or osteoporosis | 4447 (22.0) | 2221 (11.0) | 2.29 (2.16-2.42) | <.001 | 2758 (11.1) | 2012 (8.1) | 1.42 (1.33-1.51) | <.001 |
| Fractures | 1450 (7.2) | 1044 (5.2) | 1.42 (1.31-1.54) | <.001 | 1501 (6.0) | 1166 (4.7) | 1.31 (1.21-1.41) | <.001 |
| Urolithiasis | 1262 (6.3) | 470 (2.3) | 2.80 (2.51-3.12) | <.001 | 1315 (5.3) | 637 (2.6) | 2.12 (1.93-2.34) | <.001 |
| MDD | 3218 (16.0) | 2253 (11.2) | 1.51 (1.43-1.60) | <.001 | 3824 (15.4) | 2491 (10.0) | 1.63 (1.55-1.72) | <.001 |
| Anxiety disorders | 3097 (15.4) | 2177 (10.8) | 1.50 (1.41-1.59) | <.001 | 3889 (15.6) | 2772 (11.1) | 1.48 (1.40-1.56) | <.001 |
| HTN | 11 187 (55.5) | 8114 (40.2) | 1.85 (1.78-1.93) | <.001 | 11 436 (45.9) | 7813 (31.4) | 1.86 (1.79-1.93) | <.001 |
| GERD | 4602 (22.8) | 3430 (17.0) | 1.44 (1.33-1.52) | <.001 | 5035 (20.2) | 3588 (14.4) | 1.51 (1.44-1.58) | <.001 |
| Malaise or fatigue | 3687 (18.3) | 2428 (12.0) | 1.63 (1.54-1.73) | <.001 | 3812 (15.3) | 2716 (10.9) | 1.48 (1.40-1.56) | <.001 |
| Joint pain or myalgias | 6266 (31.1) | 4591 (22.8) | 1.53 (1.46-1.60) | <.001 | 6786 (27.2) | 5395 (21.7) | 1.35 (1.30-1.41) | <.001 |
| Constipation | 2335 (11.6) | 1316 (6.5) | 1.88 (1.75-2.01) | <.001 | 2447 (9.8) | 1306 (5.2) | 1.97 (1.84-2.12) | <.001 |
| Insomnia | 1592 (7.9) | 994 (4.9) | 1.65 (1.52-1.79) | <.001 | 1675 (6.7) | 1034 (4.2) | 1.67 (1.54-1.80) | <.001 |
| Polyuria | 1905 (9.4) | 1205 (6.0) | 1.64 (1.52-1.77) | <.001 | 1871 (7.5) | 1319 (5.3) | 1.45 (1.35-1.56) | <.001 |
| Weakness | 2522 (12.5) | 1670 (8.3) | 1.58 (1.52-1.77) | <.001 | 2639 (10.6) | 1690 (6.8) | 1.63 (1.53-1.74) | <.001 |
| Abdominal pain | 3979 (19.7) | 2844 (14.1) | 1.50 (1.42-1.58) | <.001 | 5188 (20.8) | 3406 (13.7) | 1.66 (1.58-1.74) | <.001 |
| Headache | 2155 (10.7) | 1453 (7.2) | 1.54 (1.44-1.65) | <.001 | 2462 (9.9) | 1636 (6.6) | 1.56 (1.46-1.67) | <.001 |
| Nausea | 1518 (7.5) | 919 (4.6) | 1.71 (1.57-1.86) | <.001 | 1795 (7.2) | 1009 (4.1) | 1.84 (1.70-1.99) | <.001 |
| Amnesia | 1484 (7.4) | 965 (4.8) | 1.58 (1.45-1.72) | <.001 | 1852 (7.4) | 1005 (4.0) | 1.91 (1.77-2.07) | <.001 |
| Gallstones | 708 (3.5) | 442 (2.2) | 1.62 (1.44-1.83) | <.001 | 866 (3.5) | 475 (1.9) | 1.85 (1.65-2.08) | <.001 |
Abbreviations: GERD, gastroesophageal reflux disease; HTN, hypertension; MDD, major depressive disorder; OR, odds ratio.
a
High risk-group 1 included a total of 20 176 patients with hypercalcemia and parathyroid hormone greater than or equal to 50 pg/mL.
b
Statistical significance is defined as P < .003.
c
High-risk group 2 included 24 905 patients with unexplained hypercalcemia and no further workup.