Hypercalcemia and osteolytic lesions as presenting symptoms of acute lymphoblastic leukemia in childhood. The use of zoledronic acid and review of the literature
-
Soultana Kolyva
Abstract
Hypercalcemia is rare in children with etiology different from adults. We report an 11.5-year-old boy with developmental delay that presented with difficulty in walking and vomiting. Laboratory investigations revealed hypercalcemia (Ca 13.8 mg/dL) with low serum parathormone, normal full blood count and no circulating blasts. Osteolytic lesions were discovered on radiological survey. Bone marrow examination was consistent with the diagnosis of common B acute lymphoblastic leukemia (ALL). Hypercalcemia was successfully treated with zoledronic acid. Hypercalcemia is a rare but well-recognized complication of ALL, usually present at the time of initial diagnosis. We reviewed the literature and analyzed the clinical and laboratory data in 36 cases of childhood ALL presenting with hypercalcemia. In conclusion, hypercalcemia alone or combined with osteolytic lesions can be the only presenting symptom of ALL in children.
References
1. Stewart AF. Clinical practice. Hypercalcemia associated with cancer. N Engl J Med 2005;352:373–9.Suche in Google Scholar
2. McKay C, Furman WL. Hypercalcemia complicating childhood malignancies. Cancer 1993;72:256–60.Suche in Google Scholar
3. Jacobs TP, Bilezikian JP. Clinical review: Rare causes of hypercalcemia. J Clin Endocrinol Metab 2005;90:6316–22.Suche in Google Scholar
4. Shane E, Dinaz I. Hypercalcemia: pathogenesis, clinical manifestations, differential diagnosis, and management. In: Favus MJ, editor. Primer on the metabolic bone diseases and disorders of mineral metabolism, 6th ed. Philadelphia: Lippincott, Williams and Wilkins, 2006:176–80.Suche in Google Scholar
5. Lietman SA, Germain-Lee EL, Levine MA. Hypercalcemia in children and adolescents. Curr Opin Pediatr 2010;22:508–15.Suche in Google Scholar
6. Myers WP. Clinical aspects and management of hypercalcemia. Med Clin North Am 1956;40:871–85.Suche in Google Scholar
7. Kerdudo C, Aerts I, Fattet S, Chevret L, Pacquement H, et al. Hypercalcemia and childhood cancer: a 7-year experience. J Pediatr Hematol Oncol 2005;27:23–7.Suche in Google Scholar
8. Kounami S, Yoshiyama M, Nakayama K, Hiramatsu S, Aoyaqi N, et al. Severe hypercalcemia in a child with acute nonlymphocytic leukemia: the role of parathyroid hormone-related protein and proinflammatory cytokines. Acta Haematol 2004;112:160–3.Suche in Google Scholar
9. Qayed M, Ahmed I, Valentini RP, Cushing B, Rajpurkar M. Hypercalcemia in pediatric acute megakaryocytic leukemia: case report and review of the literature. J Pediatr Hematol Oncol 2009;31:373–6.Suche in Google Scholar
10. Hibi S, Funaki H, Ochiai-Kanai R, Ikushima S, Todo S, et al. Hypercalcemia in children presenting with acute lymphoblastic leukemia. Int J Hematol 1997;66:353–7.Suche in Google Scholar
11. Inukai T, Hirose K, Inaba T, Kurosawa H, Hama A, et al. Hypercalcemia in childhood acute lymphoblastic leukemia: frequent implication of parathyroid hormone-related peptide and E2A-HLF from translocation 17;19. Leukemia 2007;21:288–96.Suche in Google Scholar
12. Soni PN. Hypercalcaemia and multiple osteolytic lesions in childhood acute lymphoblastic leukemia. Postgrad Med J 1993;69:483–5.Suche in Google Scholar
13. Shanks D, Linke R, Saxon B. Bones, groans and blasts. J Paediatr Child Health 2001;37:504–6.Suche in Google Scholar
14. Turker M, Oren H, Yilmaz S, Cakmakci H, Demircioglu F, et al. Unusual presentation of childhood acute lymphoblastic leukemia: a case presenting with hypercalcemia symptoms only. J Pediatr Hematol Oncol 2004;26:116–7.Suche in Google Scholar
15. Sultan I, Kraveka JM, Lazarchik J. CD19 negative precursor B acute lymphoblastic leukemia presenting with hypercalcemia. Pediatr Blood Cancer 2004;43:66–9.Suche in Google Scholar
16. Buonuomo PS, Ruggiero A, Piastra M, Riccardi R, Polidori G, et al. A case of acute lymphoblastic leukemia presenting as severe hypercalcemia. Pediatr Hematol Oncol 2004;21:475–9.Suche in Google Scholar
17. Lankisch P, Kramm CM, Hermsen D, Wessalowski R. Hypercalcemia with nephrocalcinosis and impaired renal function due to increased parathyroid hormone secretion at onset of childhood acute lymphoblastic leukemia. Leuk Lymphoma 2004;45:1695–7.Suche in Google Scholar
18. Andiran N, Alikasifoglu A, Kupeli S, Yetgin S. Use of bisphosphonates for resistant hypercalcemia in children with acute lymphoblastic leukemia: report of two cases and review of the literature. Turk J Pediatr 2006;48:248–52.Suche in Google Scholar
19. Oloomi Z. Acute lymphoblastic leukemia without circulating blasts presenting as severe hypercalcemia. Acta Med Iran 2007;45:76–8.Suche in Google Scholar
20. Mittal MK. Severe hypercalcemia as a harbinger of acute lymphoblastic leukemia. Pediatr Emerg Care 2007;23:397–400.Suche in Google Scholar
21. Bhat GM. A child with acute lymphoblastic leukemia presenting with symptomatic hypercalcemia and multiple osteolytic lesions. Indian J Med Paediatr Oncol 2007;28:46–7.Suche in Google Scholar
22. Trehan A, Cheetham T, Bailey S. Hypercalcemia in acute lymphoblastic leukemia: an overview. J Pediatr Hematol Oncol 2009;31:424–7.Suche in Google Scholar
23. Ganesan P, Thulkar S, Gupta R, Bakhshi S. Childhood aleukemic leukemia with hypercalcemia and bone lesions mimicking metabolic bone disease. J Pediatr Endocrinol Metab 2009;22:463–7.Suche in Google Scholar
24. Taskesen M, Okur N, Soker M, Tas MA. An unusual diagnosis in a child presenting with hypercalcemia: acute lymphoblastic leukemia. Gullhane Med J 2010;52:47–8.Suche in Google Scholar
25. El Saleeby CM, Grottkau BE, Friedmann AM, Westra SJ, Sohani AR. Case records of the Massachusetts General Hospital. Case 4-2011. A 4-year-old boy with back pain and hypercalcemia. N Engl J Med 2011;364:552–62.Suche in Google Scholar
26. Jamal CY, Islam MM, Rahman SA. Acute lymphoblastic leukemia presenting with severe hypercalcemia. Mymensingh Med J 2011;20:134–7.Suche in Google Scholar
27. Rizzoli R, Ferrari SL, Pizurki L, Caverzasio J, Bonjour JP. Actions of parathyroid hormone and parathyroid hormone-related protein. J Endocrinol Invest 1992;15:51–6.Suche in Google Scholar
28. Niizuma H, Fujii K, Sato A, Fujiwara I, Takeyama J, et al. PTHrP-independent hypercalcemia with increased proinflammatory cytokines and bone resorption in two children with CD19- negative precursor B acute lymphoblastic leukemia. Pediatr Blood Cancer 2007;49:990–3.Suche in Google Scholar
29. Todo S, Imashuku S, Inoda H, Yamanaka H, Hibi S, et al. Hypercalcemia in a case of childhood acute lymphoblastic leukemia. Jpn J Clin Oncol 1987;17:357–62.Suche in Google Scholar
30. Hosking DJ, Cowley A, Bucknall CA. Rehydration in the treatment of severe hypercalcaemia. J Med 1981;50:473–81.Suche in Google Scholar
31. Carano A, Teitelbaum SL, Konsek JD, Schlesinger PH, Blair HC. Bisphosphonates directly inhibit the bone resorption activity of isolated avian osteoclasts in vitro. J Clin Invest 1990;85:456–61.Suche in Google Scholar
32. Major P, Lortholary A, Hon J, Abdi E, Mills G. Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. J Clin Oncol 2001;19:558–67.Suche in Google Scholar
33. Barros ER, Saraiva GL, De Oliveira TP, Lazaretti-Castro M. Safety and efficacy of a 1-year treatment with zoledronic acid compared with pamidronate in children with osteogenesis imperfecta. J Pediatr Endocrinol Metab 2012;25:485–91.Suche in Google Scholar
34. Vuorimies I, Toiviainen-Salo S, Hero M, Makitie O. Zoledronic acid treatment in children with osteogenesis imperfecta. Horm Res Paediatr 2011;75:346–53.Suche in Google Scholar
35. August KJ, Dalton A, Katzenstein HM, George B, Olson TA, et al. The use of zoledronic acid in pediatric cancer patients. Pediatr Blood Cancer 2011;56:610–4.Suche in Google Scholar
©2014 by Walter de Gruyter Berlin Boston
Artikel in diesem Heft
- Masthead
- Masthead
- Images in pediatric endocrinology
- Leprechaunism (Donohue syndrome): report of a case in a newborn
- Original articles
- Children and adolescents with type 1 diabetes in Germany are more overweight than healthy controls: results comparing DPV database and CrescNet database
- Age of onset of pubertal maturation of Thai boys
- Plasma leptin and adiponectin concentrations correlate with cardiometabolic risk and systemic inflammation in healthy, non-obese children
- Early differentiation between good and poor response to growth hormone therapy in short children born small for gestational age (SGA) to improve the outcome of poor responders
- Children and adolescents with type 1 diabetes mellitus have a sixfold greater risk for prolonged QTc interval
- Effect of micronutrient supplementation on height velocity of underprivileged girls in comparison with un-supplemented healthy controls
- Insulin resistance in young adults born small for gestational age (SGA)
- The effect of childhood obesity on cardiac functions
- Adiponectin serum concentrations in newborn at delivery appear to be of fetal origin
- Thalassaemic Osteopathy: a cross-sectional preliminary study from Sri Lanka
- Health-related quality of life in Turner syndrome and the influence of key features
- Clinical analysis on 33 patients with hypothalamic syndrome in Chinese children
- The relationship between thyroid dose and diagnosis of primary hypothyroidism in pediatric brain tumor patients receiving craniospinal irradiation
- Molecular characterization of Chilean patients with a clinical diagnosis of Noonan syndrome
- Expensive therapies in children: benefit versus cost of combined treatment of recombinant human growth hormone and gonadotropin-releasing hormone analogue in girls with poor height potential
- The absence of mutations in homeobox candidate genes HOXA3, HOXB3, HOXD3 and PITX2 in familial and sporadic thyroid hemiagenesis
- A truncating DUOX2 mutation (R434X) causes severe congenital hypothyroidism
- Heterozygous GHR gene mutation in a child with idiopathic short stature
- A novel compound mutation of CYP27B1 in a Chinese family with vitamin D-dependent rickets type 1A
- A de novo mutation of DAX1 in a boy with congenital adrenal hypoplasia without hypogonadotropic hypogonadism
- Patient reports
- Hypercalcemia and osteolytic lesions as presenting symptoms of acute lymphoblastic leukemia in childhood. The use of zoledronic acid and review of the literature
- Preterm ovarian hyperstimulation syndrome presented with vaginal bleeding: a case report
- Pituitary stalk lesion in a 13-year-old female
- Radiologic manifestation of a BCS1L-mutated patient
- Permanent neonatal diabetes mellitus caused by a novel mutation in the KCNJ11 gene
- NKX2-1 mutations in brain-lung-thyroid syndrome: a case series of four patients
- A teenage boy with hypocalcemia after radioablation for Graves’ disease
- Short communication
- A common thyroid peroxidase gene mutation (G319R) in Turkish patients with congenital hypothyroidism could be due to a founder effect
- Letter to the Editor
- Endometriosis and migraine: what is there behind the scenes?
- 10.1515/jpem-2014-0999
Artikel in diesem Heft
- Masthead
- Masthead
- Images in pediatric endocrinology
- Leprechaunism (Donohue syndrome): report of a case in a newborn
- Original articles
- Children and adolescents with type 1 diabetes in Germany are more overweight than healthy controls: results comparing DPV database and CrescNet database
- Age of onset of pubertal maturation of Thai boys
- Plasma leptin and adiponectin concentrations correlate with cardiometabolic risk and systemic inflammation in healthy, non-obese children
- Early differentiation between good and poor response to growth hormone therapy in short children born small for gestational age (SGA) to improve the outcome of poor responders
- Children and adolescents with type 1 diabetes mellitus have a sixfold greater risk for prolonged QTc interval
- Effect of micronutrient supplementation on height velocity of underprivileged girls in comparison with un-supplemented healthy controls
- Insulin resistance in young adults born small for gestational age (SGA)
- The effect of childhood obesity on cardiac functions
- Adiponectin serum concentrations in newborn at delivery appear to be of fetal origin
- Thalassaemic Osteopathy: a cross-sectional preliminary study from Sri Lanka
- Health-related quality of life in Turner syndrome and the influence of key features
- Clinical analysis on 33 patients with hypothalamic syndrome in Chinese children
- The relationship between thyroid dose and diagnosis of primary hypothyroidism in pediatric brain tumor patients receiving craniospinal irradiation
- Molecular characterization of Chilean patients with a clinical diagnosis of Noonan syndrome
- Expensive therapies in children: benefit versus cost of combined treatment of recombinant human growth hormone and gonadotropin-releasing hormone analogue in girls with poor height potential
- The absence of mutations in homeobox candidate genes HOXA3, HOXB3, HOXD3 and PITX2 in familial and sporadic thyroid hemiagenesis
- A truncating DUOX2 mutation (R434X) causes severe congenital hypothyroidism
- Heterozygous GHR gene mutation in a child with idiopathic short stature
- A novel compound mutation of CYP27B1 in a Chinese family with vitamin D-dependent rickets type 1A
- A de novo mutation of DAX1 in a boy with congenital adrenal hypoplasia without hypogonadotropic hypogonadism
- Patient reports
- Hypercalcemia and osteolytic lesions as presenting symptoms of acute lymphoblastic leukemia in childhood. The use of zoledronic acid and review of the literature
- Preterm ovarian hyperstimulation syndrome presented with vaginal bleeding: a case report
- Pituitary stalk lesion in a 13-year-old female
- Radiologic manifestation of a BCS1L-mutated patient
- Permanent neonatal diabetes mellitus caused by a novel mutation in the KCNJ11 gene
- NKX2-1 mutations in brain-lung-thyroid syndrome: a case series of four patients
- A teenage boy with hypocalcemia after radioablation for Graves’ disease
- Short communication
- A common thyroid peroxidase gene mutation (G319R) in Turkish patients with congenital hypothyroidism could be due to a founder effect
- Letter to the Editor
- Endometriosis and migraine: what is there behind the scenes?
- 10.1515/jpem-2014-0999
