Sections

Medication

Calcimimetic agents

Class Summary

These agents increase sensitivity of the calcium-sensing receptor to extracellular calcium by changing the configuration.

Cinacalcet (Sensipar in the US, Mimpara in Europe)

View full drug information

Directly lowers iPTH levels by increasing sensitivity of calcium-sensing receptor on chief cell of parathyroid gland to extracellular calcium. Also results in concomitant decrease of serum calcium levels by affecting renal reabsorption. Indicated for secondary hyperparathyroidism in patients with chronic kidney disease. Pediatric data are limited.

Class Summary

These augment urinary elimination.

Furosemide (Lasix)

View full drug information

Used to induce calciuresis. First line for hypercalcemia with concomitant intense hydration. For IV dosing, diuretic effect begins within 5 min and peaks at 2 h.

Administer IV for emergency treatment of hypercalcemia.

Class Summary

These agents decrease serum calcium levels. They inhibit bone resorption and, thus, have a hypocalcemic effect. Used in the treatment of conditions associated with increased bone resorption, such as osteoporosis, Paget disease of bone, and management of hypercalcemia (especially that associated with malignancy). Recent reports have linked these medications with osteonecrosis of the jaw, delayed oral wound healing, and renal compromise.^[16]

Etidronate (Didronel)

View full drug information

Bisphosphonate that inhibits formation, growth, and dissolution of hydroxyapatite crystals by chemisorption to calcium phosphate surfaces; can be used IV short term or PO long term.

Pamidronate (Aredia)

View full drug information

A bisphosphonate. Same mechanism as etidronate. Inhibits formation, growth, and dissolution of hydroxyapatite crystals by chemisorption to calcium phosphate surfaces. Only IV use is approved, although a few studies have attempted PO.

Gallium nitrate (Ganite)

View full drug information

A naturally occurring heavy metal. The mechanism by which it inhibits calcium resorption from bone is unclear but may involve reducing increased bone turnover.

Class Summary

These are secreted by the thyroid gland and help maintain calcium homeostasis by increasing calcium mineral stores in bone and increasing calcium renal excretion.

Calcitonin (Calcimar, Miacalcin)

View full drug information

Acts primarily on bone but also on the kidney and GI tract to decrease serum calcium levels. Also lowers serum alkaline phosphatase levels by inhibiting bony turnover. Calcium-lowering effect begins 2 h after the first injection and lasts 6-8 h. The effect is maintained for 5-8 d.

Follow-up

[Guideline] Hawley C, Elder G. Calcium. Westmead NSW (Australia): CARI - Caring for Australasians with Renal Impairment; 2005 Oct. [Full Text].
Vezzoli G, Soldati L, Gambaro G. Roles of calcium-sensing receptor (CaSR) in renal mineral ion transport. Curr Pharm Biotechnol. Apr 2009. 10(3):302-10. [QxMD MEDLINE Link].
Sangun O, Dundar BN, Erdogan E. Severe hypercalcemia associated with Williams syndrome successfully treated with pamidronate infusion therapy. J Pediatr Endocrinol Metab. 2011. 24(1-2):69-70. [QxMD MEDLINE Link].
Lenherr-Taube N, Furman M, Assor E, et al. Mild idiopathic infantile hypercalcemia-part 2: a longitudinal observational study. J Clin Endocrinol Metab. 2021 Sep 27. 106 (10):2938-48. [QxMD MEDLINE Link].
Roizen J, Levine MA. A meta-analysis comparing the Biochemistry of Primary Hyperparathyroidism in Youths to the Biochemistry of Primary Hyperparathyroidism in Adults. J Clin Endocrinol Metab. 2014 Sep 2. jc20142268. [QxMD MEDLINE Link].
Arico M, Egeler RM. Clinical aspects of Langerhans cell histiocytosis. Hematol Oncol Clin North Am. 1998 Apr. 12(2):247-58. [QxMD MEDLINE Link].
De Sanctis V, Fiscina B, Ciccone S. Severe hypercalcemia in a patient treated for hypoparathyroidism with calcitriol. Pediatr Endocrinol Rev. 2010 Jun. 7(4):363-5. [QxMD MEDLINE Link].
Bennett MT, Sirrs S, Yeung JK, Smith CA. Hypercalcemia due to all trans retinoic acid in the treatment of acute promyelocytic leukemia potentiated by voriconazole. Leuk Lymphoma. 2005 Dec. 46(12):1829-31. [QxMD MEDLINE Link].
Picolos MK, Lavis VR, Orlander PR. Milk-alkali syndrome is a major cause of hypercalcaemia among non-end-stage renal disease (non-ESRD) inpatients. Clin Endocrinol (Oxf). 2005 Nov. 63(5):566-76. [QxMD MEDLINE Link].
Guise TA, Wysolmerski JJ. Cancer-associated hypercalcemia. N Engl J Med. 2022 Apr 14. 386 (15):1443-51. [QxMD MEDLINE Link].
Hsu YH, Chen HI. Acute respiratory distress syndrome associated with hypercalcemia without parathyroid disorders. Chin J Physiol. Dec 2008. 51(6):414-8. [QxMD MEDLINE Link].
Balentine CJ, Xie R, Kirklin JK, Chen H. Failure to Diagnose Hyperparathyroidism in 10,432 Patients With Hypercalcemia: Opportunities for System-level Intervention to Increase Surgical Referrals and Cure. Ann Surg. 2017 Jul 3. [QxMD MEDLINE Link].
Baroncelli GI, Bertelloni S. The Use of Bisphosphonates in Pediatrics. Horm Res Paediatr. 2014 Nov 6. 290-302. [QxMD MEDLINE Link].
Gatti D, Viapiana O, Idolazzi L, Fracassi E, Adami S. Neridronic acid for the treatment of bone metabolic diseases. Expert Opin Drug Metab Toxicol. Oct 2009. 5(10):1305-11. [QxMD MEDLINE Link].
Faggiano A, Tavares LB, Tauchmanova L, Milone F, Mansueto G, Ramundo V et al. Effect of treatment with depot somatostatin analogue octreotide on primary hyperparathyroidism in MEN1 patients. Clin Endocrinol. May 2008. Epub:[QxMD MEDLINE Link].
Landesberg R, Cozin M, Cremers S, Woo V, Kousteni S, Sinha S, et al. Inhibition of oral mucosal cell wound healing by bisphosphonates. J Oral Maxillofac Surg. May 2008. 66(5):839-47. [QxMD MEDLINE Link].
Oski F, DeAngelis CD, Feigin RD. Principles and Practice of Pediatrics. 2nd ed. 1994.

Media Gallery

Investigations flowchart.

of 1

Table.

Laboratory Test	Reference Range	Normal Response to Increased Calcium
Serum calcium	8.5-10.2 mg/dL	NA
Ionized calcium	1-1.3 mmol/L	NA
PTH (intact)	10-55 pg/mL*	Decrease
Serum phosphate	Age-dependent	Increase
1,25-dihydroxyvitamin D	36-108 pmol/L	Decrease
Alkaline phosphatase	68-217 U/L	Normal
Urine calcium	4 mg/kg/d	Increase
Urine Ca/Cr ratio	See note†	Increase
Urine cAMP‡	< 5 mol	Decrease
*Note that 1 mmol/L equals 4 mg/dL. †In infants younger than 7 months, the reference range is less than 0.86; in infants aged 7-18 months, the reference range is less than 0.6. By age 6-7 years, the adult reference range of less than 0.21 is reached.‡The urine cAMP level generally parallels the PTH level.

Table.

Condition	Serum Phosphorus	Serum Alkaline Phosphatase	Urine Calcium	Urine Phosphate	PTH
Hyperparathyroidism	Low	Normal-high	High*	High	High
Vitamin D excess	Normal-high	Low	High	High
Malignancy	Often low	High †	Variable	High
Granulomatous disease	Normal-high	Normal-high	High	Normal
Milk alkali syndrome	Normal-high	Normal	Normal	Normal
FHH	Normal or low	Normal	Low (< 200mg/d)	Normal	Low
*67% of the time † Except hematologic malignancies, in which alkaline phosphatase is normal

Back to List

Author

Pisit (Duke) Pitukcheewanont, MD Associate Professor of Clinical Pediatrics, University of Southern California, Keck School of Medicine, Childrens Hospital Los Angeles

Pisit (Duke) Pitukcheewanont, MD is a member of the following medical societies: American Academy of Pediatrics, American Diabetes Association, American Medical Association, American Society for Bone and Mineral Research, Endocrine Society, Pediatric Endocrine Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London) Professor and Chair, First Department of Pediatrics, Athens University Medical School, Aghia Sophia Children's Hospital, Greece; UNESCO Chair on Adolescent Health Care, University of Athens, Greece

George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London) is a member of the following medical societies: American Academy of Pediatrics, American College of Physicians, American Pediatric Society, American Society for Clinical Investigation, Association of American Physicians, Endocrine Society, Pediatric Endocrine Society, Society for Pediatric Research, American College of Endocrinology

Disclosure: Nothing to disclose.

Chief Editor

Sasigarn A Bowden, MD, FAAP Professor of Pediatrics, Section of Pediatric Endocrinology, Metabolism and Diabetes, Department of Pediatrics, Ohio State University College of Medicine; Pediatric Endocrinologist, Division of Endocrinology, Nationwide Children’s Hospital; Affiliate Faculty/Principal Investigator, Center for Clinical Translational Research, Research Institute at Nationwide Children’s Hospital

Sasigarn A Bowden, MD, FAAP is a member of the following medical societies: American Society for Bone and Mineral Research, Central Ohio Pediatric Society, Endocrine Society, International Society for Pediatric and Adolescent Diabetes, Pediatric Endocrine Society, Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

Ilene A Claudius, MD Assistant Professor of Pediatrics, Division of Emergency Medicine, Children's Hospital, Los Angeles

Ilene A Claudius, MD is a member of the following medical societies: Alpha Omega Alpha

Disclosure: Nothing to disclose.

Thomas A Wilson, MD Professor of Clinical Pediatrics, Chief and Program Director, Division of Pediatric Endocrinology, Department of Pediatrics, The School of Medicine at Stony Brook University Medical Center

Thomas A Wilson, MD is a member of the following medical societies: Endocrine Society, Pediatric Endocrine Society, Phi Beta Kappa

Disclosure: Nothing to disclose.

Jon Nakamoto, MD Consulting Staff, Department of Pediatric Endocrinology, Quest Diagnostics

Jon Nakamoto, MD is a member of the following medical societies: Alpha Omega Alpha

Disclosure: Nothing to disclose.

Acknowledgements

Oved Fattal, MD Staff Physician, Department of Pediatrics, Kaiser Permanente Medical Group

Oved Fattal, MD is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Pediatric Hypercalcemia Medication

Calcimimetic agents

Class Summary

Cinacalcet (Sensipar in the US, Mimpara in Europe)

Cinacalcet (Sensipar in the US, Mimpara in Europe)

Loop diuretics