Approaching hypercalcemia in monoclonal gammopathy of undetermined significance: insights from the iStopMM screening study

Ástrún Helga Jónsdóttir (1Faculty of Medicine, University of Iceland, Reykjavik, Iceland) H Helga Ágústa Sigurjónsdóttir (1Faculty of Medicine, University of Iceland, Reykjavik, Iceland) S Sigrún Thorsteinsdóttir T Thorir Einarsson Long (1Faculty of Medicine, University of Iceland, Reykjavik, Iceland) I Ingigerður Sólveig Sverrisdóttir (1Faculty of Medicine, University of Iceland, Reykjavik, Iceland) E Elias Eythorsson (1Faculty of Medicine, University of Iceland, Reykjavik, Iceland) J Jón Þórir Óskarsson (1Faculty of Medicine, University of Iceland, Reykjavik, Iceland) R Runolfur Palsson (1Faculty of Medicine, University of Iceland, Reykjavik, Iceland) O Olafur Skuli Indridason (8Department of Nephrology, Landspítali University Hospital, Reykjavik, Iceland) B Brynjar Viðarsson (9Department of Hematology Landspítali University Hospital, Reykjavik, Iceland) P Pall Torfi Onundarson (1Faculty of Medicine, University of Iceland, Reykjavik, Iceland) Ísleifur Ólafsson (7Department of Clinical Biochemistry and Hematology, Landspítali University Hospital, Reykjavik, Iceland) I Ingunn Þorsteindóttir (7Department of Clinical Biochemistry and Hematology, Landspítali University Hospital, Reykjavik, Iceland) B Bjarni A. Agnarsson (1Faculty of Medicine, University of Iceland, Reykjavik, Iceland) M Margrét Sigurðardóttir (10Department of Pathology, Landspítali University Hospital, Reykjavik, Iceland) Ásbjörn Jónsson (11Department of Radiology, Akureyri Hospital, Akureyri, Iceland) M Malin Hultcrantz (1Memorial Sloan Kettering Cancer Center, Myeloma Service, Department of Medicine, New York, United States) B Brian G. M. Durie S Stephen Harding (2The Binding Site (part of Thermo Fisher Scientific), Birmingham, United Kingdom) O Ola Landgren T Thorvardur Jon Love (1Faculty of Medicine, University of Iceland, Reykjavik, Iceland) S Sigurður Yngvi Kristinsson S Sæmundur Rögnvaldsson

Abstract

Abstract Hypercalcemia in monoclonal gammopathy of undetermined significance (MGUS) presents a clinical challenge because it may indicate progression to multiple myeloma (MM) but could also be due to a multitude of unrelated disorders. To inform the approach to this clinical challenge, we conducted a nested cohort study within the Iceland Screens, Treats, or Prevents Multiple Myeloma screening study. Of the 75 422 Icelanders aged 40 years and above who underwent screening for MGUS, we included 2546 with MGUS who were in active follow-up, including regular serum calcium measurements. In total, 191 individuals (7.5%) had hypercalcemia detected at least once, of whom 93 had persistent hypercalcemia (48.7%). MM was found in 3 participants with persistent hypercalcemia (3.2%); all had concurrent bone disease and other end-organ damage. The most common causes of hypercalcemia were primary hyperparathyroidism (56.0%) and malignancies other than MM (16.0%). In this first comprehensive study on hypercalcemia in MGUS, we observed that hypercalcemia rarely indicated MGUS progression and never in the absence of other symptoms of MM. More than half of hypercalcemia cases were transient, and the underlying causes were similar to those in the general population. We conclude that hypercalcemia in MGUS should be approached in the same way as in those without MGUS.

Article Details

Journal Blood
Volume / Issue Vol. 145, Issue 9
Published February 27, 2025
Pages 970-974
ISSN 0006-4971
Publisher Elsevier BV

Journal Info

Blood

Elsevier BV

ISSN: 0006-4971 Health Sciences

Authors (23)

Ástrún Helga Jónsdóttir

1Faculty of Medicine, University of Iceland, Reykjavik, Iceland

H

Helga Ágústa Sigurjónsdóttir

1Faculty of Medicine, University of Iceland, Reykjavik, Iceland

S

Sigrún Thorsteinsdóttir

T

Thorir Einarsson Long

1Faculty of Medicine, University of Iceland, Reykjavik, Iceland

I

Ingigerður Sólveig Sverrisdóttir

1Faculty of Medicine, University of Iceland, Reykjavik, Iceland

E

Elias Eythorsson

1Faculty of Medicine, University of Iceland, Reykjavik, Iceland

J

Jón Þórir Óskarsson

1Faculty of Medicine, University of Iceland, Reykjavik, Iceland

R

Runolfur Palsson

1Faculty of Medicine, University of Iceland, Reykjavik, Iceland

O

Olafur Skuli Indridason

8Department of Nephrology, Landspítali University Hospital, Reykjavik, Iceland

B

Brynjar Viðarsson

9Department of Hematology Landspítali University Hospital, Reykjavik, Iceland

P

Pall Torfi Onundarson

1Faculty of Medicine, University of Iceland, Reykjavik, Iceland

Ísleifur Ólafsson

7Department of Clinical Biochemistry and Hematology, Landspítali University Hospital, Reykjavik, Iceland

I

Ingunn Þorsteindóttir

7Department of Clinical Biochemistry and Hematology, Landspítali University Hospital, Reykjavik, Iceland

B

Bjarni A. Agnarsson

1Faculty of Medicine, University of Iceland, Reykjavik, Iceland

M

Margrét Sigurðardóttir

10Department of Pathology, Landspítali University Hospital, Reykjavik, Iceland

Ásbjörn Jónsson

11Department of Radiology, Akureyri Hospital, Akureyri, Iceland

M

Malin Hultcrantz

1Memorial Sloan Kettering Cancer Center, Myeloma Service, Department of Medicine, New York, United States

B

Brian G. M. Durie

S

Stephen Harding

2The Binding Site (part of Thermo Fisher Scientific), Birmingham, United Kingdom

O

Ola Landgren

T

Thorvardur Jon Love

1Faculty of Medicine, University of Iceland, Reykjavik, Iceland

S

Sigurður Yngvi Kristinsson

S

Sæmundur Rögnvaldsson