Hypercalcemia is a common medical problem with an estimated prevalence of 15% among hospitalized patients. Multiple myeloma (MM) and primary hyperparathyroidism (PHPT) are among the most common causes of hypercalcemia but coexistence of both pathologic processes in a patient is an extremely rare phenomenon. In this paper we have discussed a patient presenting with this rare phenomenon. We have also provided a comprehensive review of the scientific literature published on codiagnosis of MM and PHPT.
Hypercalcemia is a common clinical problem with an estimated prevalence of 15% among hospitalized patients [
A 92-year-old Caucasian female with a past medical history of Alzheimer’s dementia, seizure disorder, osteoporosis, and osteoarthritis was admitted to the hospital for an evaluation of a new onset confusion and constipation. Review of symptoms during admission was significant for anorexia, weight loss, constipation for the last three weeks, and history of a fall one month prior to the presentation. Family history was significant for MM in a sister. At the time of presentation, the patient was using donepezil, memantine, vitamin D with calcium, calcium carbonate (calcium containing antacid), and levetiracetam. Vitals at the time of admission were blood pressure 140/58, pulse 68, respiratory rate 18, oxygen saturation 98% on room air, and temperature 97.4. On physical examination, the patient was alert and oriented in place and person but not in time. Other significant findings were diastolic murmur in right second intercostal space, petechiae over lower extremities, and back tenderness, which the patient attributed to a recent fall. Lumbar spine X-ray was done three weeks prior to the presentation that showed degenerative changes with no evidence of fracture. Basic blood workup including complete blood count and comprehensive metabolic panel was done, which revealed anemia, leucopenia, and hypercalcemia. Home medications were held for concerns of hypercalcemia and confusion.
Endocrinology and neurology services were consulted. MRI of the brain was done, which showed lytic lesions as shown in Figure
Result name | Results | Reference range |
| ||
WBC | 2.9 K/mm cu | 4.2–11.0 |
Platelet | 156 K/mm cu | 140–400 |
Hemoglobin Hb | 9.0 g/dL | 12.0–15.0 |
Hematocrit | 27.1% | 36.0–47.0 |
Reticulocyte | 0.7% | 0.5–2.8 |
Blood urea nitrogen | 22 mg/dL | 5–20 |
Creatinine | 1.11 mg/dL | 0.0–1.00 |
Sodium | 143 mmol/L | 135–145 |
Potassium | 4.0 mmol/L | 3.4–5.1 |
Chloride | 104 mmol/L | 98–109 |
Bicarbonate | 33 mmol/L | 23–31 |
Calcium | 13.3 mg/dL | 8.4–10.5 |
Total protein | 7.0 g/dL | 6.4–8.3 |
Albumin | 4.0 g/dL | 3.4–5.2 |
Aspartate amino transferase | 20 IU/L | 0–32 |
Alanine amino transferase | 10 IU/L | 0–40 |
Alkaline phosphatase | 67 IU/L | 35–104 |
Bilirubin total | 0.2 mg/dL | 0–10.0 |
Haptoglobin | 157 mg/dL | 36–195 |
Vitamin B12 | 532 pg/mL | 211–946 |
TSH | 1.160 uIU/mL | 0.400–5.400 |
Vitamin D25 OH | 47.0 ng/mL | 30.0–100.0 |
25 Hydroxy D3 | 26 pg/mL | |
25 hydroxy D2 | <8 | |
Vitamin D 1,25(OH)2 | 26 | 18–72 |
Folate | >20.0 ng/mL | 3.1–17.5 |
Ferritin | 64 ng/mL | 13–150 |
Phosphorous | 2.8 mg/dL | 2.0–4.0 |
Lactate dehydrogenase | 137 IU/L | 135–214 |
Total iron | 30 ug/dL | 30–160 |
Unsaturated IBC | 234.0 ug/dL | 110.0–370.0 |
Total IBC | 264.0 | 228.0–428.0 |
Percentage of iron saturation | 11% | 20–55 |
PTH intact on day of presentation | 70.5 pg/mL | 15.0–65.0 |
PTH 7 months later | 540.0 pg/mL | |
PTH-related protein | 18 pg/mL | 14–27 |
Beta-2 microglobulin | 3.3 mg/L (5.8 mg/L four months later) | 0.8–2.2 |
Serum viscosity | 1.5 relative to H2O | 1.5–1.9 |
PT/INR | 10.6/1.0 sec | 9.211.8/0.9–1.1 |
APTT | 29 sec | 24–33 |
Immunoglobulins | ||
IGA | 29 mg/dL | 50–400 |
IGG | 692 mg/dL (1200, 5 months later) | 600–1500 |
IGM | 6 mg/dL | 50–300 |
Free kappa light chains | 1510 | 3.3–19.4 mg/L |
Free lambda light chains | 2.4 | 5.7–26.3 |
Free Kappa/lambda | 629.17 | 0.26–1.65 |
Urine protein electrophoresis | ||
Urine volume 24 hours | 1150 mL/24 hour | |
Urine-protein electrophoresis (UPE) | 253 mg/24 hour | 0–165 |
Albumin UPE | 30.6% | |
Alpha1 | 16.1% | |
Alpha2 | 14.1% | |
Beta | 17.1% | |
Gamma | 22.1% | |
Immunofixation | Free kappa light chains | |
24-hour-urine protein | 310.5 mg/24 hour | 0–150 |
24-hours-urine creatinine | 0.7 g/24 hour | 0.74–1.57 |
24-hour-urine volume | 1150 cc | |
24-hour-urine creatinine | 0.5 g/24 hour | 0.74–1.57 |
24-hour-urine volume | 900 mL (repeat test) | |
24-hour-urine calcium | 239 mg/24 hour | 100–300 |
Serum protein electrophoresis | ||
Albumin | 3.3 g/dL | 3.1–5.0 |
Alpha 1 | 0.3 g/dL | 0.2–0.5 |
Alpha2 | 0.7 g/dL | 0.5–1.1 |
Beta | 0.6 g/dL | 0.6–1.1 |
Gamma | 1.5 g/dL | 0.7–1.7 |
Albumin/globulin | 1.0 | |
M spike | 1.09 g/dL | |
Total protein | 6.5 g/dL | 6.4–8.3 |
Immunofixation | Monoclonal paraprotein of class IgG kappa | |
CD56 NK cells | 63% | 3–35 |
CD 138 marker | 26% | |
Lambda B-cell marker | 1% | 1–7 |
Kappa B-cell marker | 73% | 2–14% |
CD45 LCA | 98% | 92–100 |
CD38 Marker | 26% | 1–17 |
MRI demonstrating lytic lesions.
Mildly hypercellular bone marrow with plasmacytosis (30%), consistent with multiple myeloma.
Skeletal survey showing lytic lesions in long bones and skulls.
Hypercalcemia was managed with intravenous hydration, calcitonin, bisphosphonates, and furosemide. The patient was started on melphalan and prednisone, which were later switched to lenalidomide with a high dose of dexamethasone due to a poor treatment response. After one and a half year, the patient is still following in our outpatient oncology center being on a low dose of lenalidomide with a stable M protein.
Hypercalcemia is common in patients with MM and occurs in 28% of myeloma cases [
Clubb et al. [
PHPT leads to hypercalcemia via direct bone resorption [
The above-mentioned pathogenic mechanism gives an insight to how PHPT and MM may be linked. Some studies have suggested that calcium may act as a mitogenic factor [
Summary of published cases [
|
Author | Age/ Gender | Type of MM | Ca (mg/dL) | Therapy for MM and PHPT | Parathyroid histology | Outcome | Initial diagnosis |
---|---|---|---|---|---|---|---|---|
1 |
Pest et al. [ |
76 F | IgA-? | 13.2 | Hydration, bisphosphonates, Lasix, melphalan, cyclophosphamide, and steroids | Adenoma | Survived | PHPT |
2 |
Rao et al. [ |
54 M | IgG-lambda | 11.2 | Adriamycin, melphalan, prednisone, cyclophosphamide, and parathyroidectomy | Adenoma | Died after 12 years | Both |
3 |
Jackson and Orland [ |
45 F | IgG-lambda | 17.1 | Hydration, Lasix, prednisone, and melphalan | Adenoma | — | MM |
4 |
Chisholm et al. [ |
80 M | Kappa | 13.1 | Parathyroidectomy, radiotherapy, melphalan, prednisone, vincristine, carmustine, cyclophosphamide, hydration, and Lasix | Adenoma (c-cells) | Died 2 years later | PHPT |
5 |
Francis et al. [ |
70F | Lambda | 11.6 | Norethisterone, vincristine, melphalan, and prednisone | Adenoma | Died 3 weeks later | PHPT |
6 |
Mundis and kyle [ |
76 F | IgG-kappa | 11.0 | Melphalan, prednisone, and parathyroidectomy | Adenoma (c-cells) | survived | MM |
7 |
Stone et al. [ |
47 F | IgA-kappa | 13.7 | Melphalan, prednisone, radiotherapy, parathyroidectomy, hydration, and mithramycin | Adenoma | Died | MM |
8 |
Hoelzer and Silverberg [ |
51 F | IgA-lambda | 11.9 | Parathyroidectomy? | Adenoma (c-cells) | — | PHPT |
9 |
Schneider and Thomas [ |
74 F | IgG-kappa | 12.0 | Melphalan, prednisone, and parathyroidectomy | Adenoma | Survived | MM |
10 |
Toussirot et al. [ |
82 M | Kappa | 15.2 | Melphalan, prednisone, and parathyroidectomy | Hyperplasia | Died | PHPT |
11 |
Goto et al. [ |
73 F | Kappa | 13.2 | Parathyroidectomy, melphalan | Adenoma | Died 1 year later | PHPT |
12 |
Otsuka et al. [ |
77 F | IgG-lambda | Melphalan, prednisone, bisphosphonates, calcitonin, and parathyroidectomy | c-cells hyperplasia | Survived | — | |
13 |
Fery-Blanco et al. [ |
68 F | IgG-kappa | 11.28 | ? chemotherapy and surgery refused | Adenoma | Died | Both |
14 |
Sarfati et al. [ |
62 F | IgA-kappa | 16.4 | Mithramycin, lasix, plasmaphoresis, Adriamycin, vincristine, prednisone, and parathyroidectomy | Adenoma | Survived | MM |
15 |
Rosen et al. [ |
81 M | IgG-kappa | 13.4 | Hydration, bisphosphonates, melphalan, prednisone, radiotherapy, needle aspiration of parathyroid gland, and refused surgery | Adenoma | Survived | MM |
16 |
Tomon et al. [ |
60 F | IGA-kappa | — | — | — | — | MM |
17 |
Fanari et al. [ |
59 F | lambda | 12.7 | Hydration, bisphosphonates, cinacalcet, bortezomib and dexamethasone | Possible Adenoma | Died 4 months later | Both |
18 |
Bogas et al. [ |
72 F | IgG-kappa | 13.66 | Melphalan, prednisone, and Interferon? | Adenoma | Died 4 years later | Both |
19 |
Katayama et al. [ |
50 F | PHPT | |||||
20 |
Romagnoli et al. [ |
70 F | — | — | Parathyroidectomy, steroids and chemotherapy | Adenoma | — | PHPT (MEN-1) |
21 |
Toh and Winocour et al. [ |
71 M | 12.0 | Melphalan, prednisone, and bisphosphonates | Died 6 weeks later | MM | ||
22 |
Sope |
77 F | Kappa (ns) | 12.9 | Bisphosphonates, refused surgery, or chemotherapy | Died 1 year later | Both | |
23 |
Khandwala and Boctor [ |
72 F | — | 11.7/ 16.6* | Parathyroidectomy, bisphosphonates, calcitonin, melphalan, and prednisone | Adenoma | — | PHPT |
24 |
Patel et al. [ |
73 F | IgG- kappa | 13.5 | Bisphosphonates, steroids, thalidomide, plicamycin, and parathyroidectomy | Adenoma | — | MM |
25 |
Avcioglu et al. [ |
52 F | IgG-kappa | 12.6 | Parathyroidectomy and steroids | Adenoma | — | Both |
26 |
Chowdhury and Scarsbrook et al. [ |
87 F | — | — | — | — | — | PHPT |
27 |
Dalgleish and Gatenby [ |
59 F | IgG-lambda | 11.68 | Hydration, lasix, prednisone, mithramycin, cyclophosphamide, and parathyroidectomy | Adenoma | Survived | MM |
28 |
Peters et al. [ |
73 M | IgA-lambda | 16 | Parathyroidectomy, chemotherapy, and radiotherapy | Hyperplasia | Died 1 week later | PHPT |
29 | Our case | 92 F | IgG-kappa | 13 .3 | Bisphosphonates, Lasix, hydration, calcitonin, melphalan, prednisone, lenalidomide, and dexamethasone | — | Survived | Both |
30 |
Johansson and Werner [ |
A search for concomitant cause of hypercalcemia should be pursued in cases of difficult-to-control hypercalcemia and in elderly individuals, in whom the incidence of PTHP and MM is common.