Abstract.
Severe symptomatic hypercalcemia is a rare event in children with malignancies. Up to now there is limited experience treating childhood hypercalcemia with bisphosphonates in addition to calcitonin. We report a 5-year-old boy with acute lymphoblastic lymphoma who presented with malignant hypercalcemia at diagnosis. The maximal serum calcium concentration was 15.2 mg/dl (3.81 mmol/l). Conventional therapy with forced diuresis and furosemide failed. Calcitonin (10 IU/kg/24 h i.v. for 2 days) and pamidronate (1 mg/kg over 2 hours i.v.) were used successfully without adverse effect lowering the serum calcium level within 24 hours to normal values. We recommend the use of calcitonin and pamidronate as first-line therapy together with forced diuresis and furosemide in childhood hypercalcemia secondary to malignancies as it is rapidly effective and has no significant side effects.
Hyperkalzämie ist ein seltenes Ereignis bei Kindern mit malignen Erkrankungen. Bis jetzt gibt es nur wenig Erfahrung, eine Hyperkalzämie im Kindesalter mit Pamidronat zusätzlich zu Calcitonin zu behandeln. Wir berichten über einen 5-jährigen Jungen mit akuter lymphatischer Leukämie, der bei Diagnosestellung der malignen Erkrankung eine symptomatische Hyperkalzämie zeigte. Die maximale Kalziumkonzentration im Serum war 15,2 mg/dl (3,81 mmol/l). Konventionelle Therapie mit Wässerung und Furosemid zeigte keinen Erfolg. Durch den Einsatz von Calcitonin (10 E/kg/24 Stunden i.v. für 2 Tage) und Pamidronat (1 mg/kg in 2 Stunden i.v.) konnte der Kalziumspiegel innerhalb von 24 Stunden in Normbereiche gesenkt werden. Es traten keine schweren Nebenwirkungen auf. Wir empfehlen den primären Einsatz von Calcitonin und Pamidronat zusätzlich zu forcierter Diurese und Furosemid bei Kindern mit symptomatischer Hyperkalzämie bedingt durch eine Krebserkrankung.
Key words:
Cancer-related hypercalcemia - childhood - pamidronate - calcitonin
Schlüsselwörter:
Hyperkalzämie durch maligne Erkrankun-gen - Kinder - Pamidronat - Calcitonin
Literatur
01
Blind E, Raue F, Meinel T, Wüster C, Ziegler R.
Levels of parathyroid hormone-related protein (PTHrP) in hypercalcemia of malignancy are not lowered by treatment with the bisphosphonate BM 21.0955.
Horm Metab.
1993;
25
40-44
02
Boudaillez B R, Pautard B J, Sebert J, Kremp O, Piussan C X.
Leukemia-associated hypercalcemia in a 10-year-old boy: Effectiveness of aminohydroxypropylidene bisphosphonate.
Pediatr Nephrol.
1990;
4
510-511
03
Burtis W J, Brady T G, Orloff J J, Ersbak J B, Warrell R P Jr, Olson B R, Wu T L, Mitnick M E, Broadus A E, Stewart A F.
Hormone-related protein in patients with humoral hypercalcemia in cancer.
N Engl J Med.
1990;
32
1106
04
Chisholm M A, Mulloy A L, Taylor A T.
Acute management of cancer-related hypercalcemia.
Ann of Pharmacotherapy.
1996;
30
507-513
05
De Graaf J H, Tamminga R Y, Kamps W A.
Paraneoplastic manifestations in children.
Eur J Pediatr.
1994;
153
784-791
06
Gucalp R, Ritch O, Wiernik P H, Sarma P R, Keller A, Richman S P, Tauer K, Neidhart J, Mallette L E, Siegel R, VandePol C J.
Comparative study of pamidronate disodium and etidronate disodium in the treatment of cancer-related hypercalcemia.
J Clin Oncol.
1992;
10
134-142
07
Hibi S, Funaki H, Ochiai-Kanai R, Ikushima S, Sawada T, Imashuku S.
Hypercalcemia in children presenting with acute lymphoblastic leukemia.
Int J Hematol.
1997;
66
353-357
08
Jansson S, Tissell L E, Lindstedt G, Lundberg P A.
Disodium pamidronate in the preoperative treatment of hyerpcalcemia in patients with primary hyperparathyroidism.
Surgery.
1991;
110
480-486
09
Kawasaki H, Takayama J, Nagasaki K, Yamaguchi K, Ohira M.
Hypercalcemia in children with rhabdomyosarcoma.
J Pediatr Hematol Oncol.
1998;
20
327-329
10
Kinirons M T.
Newer agents for the treatment of malignant hypercalcemia.
Am J Med Sci.
1993;
305
403-406
11
Kutluk M T, Akyuz C, Yalcin B, Varan A, Büyükpamukucu M.
Use of pamidronate in the management of acute cancer-related hypercalcemia in children [letter; comment].
Med Pediatr Oncol.
1998;
31
39
12
Kutluk M T, Hazar V, Akyüz C, Varan A, Büyükpamukcu M.
Childhood cancer and hypercalcemia: report of a case treated with pamidronate.
J Pediatr.
1997;
130
828-831
13
Leblanc A, Caillaud J M, Hartmann O, Kalifa C, Flamant F, Patte C, Tournade M F, Lemerle J.
Hypercalcemia preferentially occurs in unusual forms of childhood non-Hodgkin's lymphoma, rhabdomyosarcoma, and Wilms tumor.
Cancer.
1984;
54
2132-2136
14
Lteif A N, Zimmerman D.
Bisphosphonates for treatment of childhood hypercalcemia.
Pediatrics.
1998;
102
990-993
15
McIntyre H D, Cameron D P, Urquhart S M, Davie W E.
Immobilization hypercalcemia responding to intravenous pamidronate sodium therapy.
Postgrad Med J.
1989;
65
244-246
16
McKay C, Furman W L.
Hypercalcemia complicating childhood malignancies.
Cancer.
1993;
72
256-260
17
Mundy G R, Ibbotson K J, D'Souza S M, Simpson E L, Jacobs J W, Martin T J.
The hypercalcemia of cancer. Clinical implications and pathogenic mechanisms.
N Engl J Med.
1984;
310
1718-1727
18
Nussbaum S R, Younger J, Vandepol C J, Gagel R F, Zubler M A, Chapman R, Henderson I C, Mallette L E.
Single-dose intravenous therapy with pamidronate for the treatment of hypercalcemia of malignancy: comparison of 30-, 60-, 90-mg dosages.
Am J Med.
1993;
95
297-304
19
Profumo R J, Reese J C, Fay T M, Garibaldi L R, Kane R E.
Severe immobilization induced hypercalcemia in a child after liver transplantation successfully treated with pamidronate.
Transplantation.
1994;
57
301-303
20
Purohit O P, Anthony C, Radstone C R, Owen J, Coleman R E.
High-dose intravenous pamidronate for metastatic bone pain.
Br J Cancer.
1994;
70
554-558
21
Ralston S H, Gallaher S J, Patel U, Dryburgh F J, Fraser W, Cowan R A, Boyle I T.
Comparison of three intravenous bisphosphonates in cancer-associated hypercalcemia.
Lancet.
1989;
2
1180-1182
22
Ralston S H, Thiebaud D, Herrmann Z, Steinhauer E U, Thurlimann B, Walls J, Lichinitser M R, Rizzoll R, Hagberg H, Huss H J, Tubiana Hulin M, Body J J.
Dose-response study of ibandronate in the treatment of cancer-associated hypercalcemia.
Br J Cancer.
1997;
75
295-300
23
Sekine M, Takami H.
Combination of calcitonin and pamidronate for emergency treatment of malignant hypercalcemia.
Oncol Rep.
1998;
5
197-199
24
Tagaki M, Takahiashi K, Maruyama T, Kaneko K, Obinata K, Tadokoro R, Kastumata K, Miura Y, Fujita H, Tokita A, Ishimoto K, Yabuta K.
Acute lymphoblastic leukemia accompanied by severe hypercalcemia: successful treatment including aminohydroxypropylidene bisphosphonate (pamidronate disodium) [letter].
Pediatr Hematol Oncol.
1998;
15
283-286
25
Varache N, Audran M, Clochon P, Lortholary A, Bouachour G, Alquier P, Basle M F.
Aminohydroxypropylidene bisphosphonate treatment of severe immobilization hypercalcemia in a young patient.
Clin Rheumatol.
1991;
10
328-332
26
Warrell R P Jr, Alcock N W, Bockman R S.
Gallium nitrate inhibits accelerated bone turnover in patients with bone metastasis.
J Clin Oncol.
1987;
5
292-298
27
Williams C JC, Smith R A, Ball R J, Wilkinson H.
Hypercalcemia in osteogenesis imperfecta treated with pamidronate.
Arch Dis Child.
1997;
76
169-170
28
Yamaguchi K, Grant J, Noble-Jamieson G, Jamieson N, Barnes N D, Compston J E.
Hypercalcemia in primary oxalosis: role of increased bone resorption and effects of treatment with pamidronate.
Bone.
1995;
6
61-67
29
Young G, Shende A.
Use of Pamidronate in the management of acute cancer-related hypercalcemia in children.
Med Ped Oncol.
1998;
30
117-121
Dr. Irene Schmid
Kinderklinik und KinderpoliklinikDr. von Haunersches KinderspitalUniversität München
Lindwurmstr. 4
80337 München
Telefon: Tel. 0 89-51 60-28 42
Fax: Fax 0 89-51 60-47 19
eMail: E-mail: Irene.Schmid@kk-i.med.uni-muenchen.de