Pediatric Hyperparathyroidism Treatment & Management
- Author: Gordon L Klein, MD, MPH; Chief Editor: Stephen Kemp, MD, PhD more...
Medical management of primary hyperparathyroidism has not been satisfactory because no agents are available that can produce either sustained blockage of parathyroid hormone (PTH) release by parathyroid glands or sustained blockage of hypercalcemia. However, research is currently underway to develop calcimimetics, which can stimulate upregulation of parathyroid calcium-sensing receptor and potentially blunt abnormally increased PTH secretion.
Clinical studies have already identified the drug cinacalcet, which can treat both primary and secondary hyperparathyroidism in adults as well as at least one recent report of its successful use in children. Muscheites et al in Germany used a daily dosage of 0.25 mg/kg body weight for 4 weeks in 7 children with end-stage renal disease and secondary hyperparathyroidism, with a resultant 80% decrease in serum intact PTH levels. In addition, human osteoprotegerins, which can block PTH-induced hypercalcemia, are also undergoing clinical studies. Another drug that currently shows promise in treating osteoporosis but has not yet been studied in either primary or secondary hyperparathyroidism is denosumab, a monoclonal antibody against RANK ligand. This drug is effective in blocking bone resorption.
For secondary hyperparathyroidism that occurs with chronic renal failure, parenteral administration of calcitriol is helpful; however, this manner of administration is feasible only for patients receiving hemodialysis. One complication of intravenous calcitriol may be an increase in circulating calcium. This can be avoided by intravenous administration of a new vitamin D analog, paricalcitol, which can treat secondary hyperparathyroidism without raising serum calcium and phosphorus levels.
For individuals receiving therapy with peritoneal dialysis, oral administration of calcitriol is the only alternative. This route of administration may not be as effective as the intravenous route; however, some preliminary clinical trials, as stated above, have been conducted for calcimimetics in primary and secondary hyperparathyroidism. Early results are encouraging. In addition, a new oral form of paricalcitol is now in development and may reduce circulating PTH an average of 42%.
For other forms of secondary hyperparathyroidism, such as that resulting from chronic cholestatic liver disease, no standard treatment guidelines are available. Therefore, treatment should be aimed at ameliorating the underlying condition and supplying sufficient dietary calcium, phosphorus, vitamin D, and magnesium. This ensures that hyperparathyroidism is not exacerbated by nutritional insufficiency.
The treatment of acute severe hypercalcemia (serum calcium level >14 mg/dL), which may or may not result from hyperparathyroidism, includes hydration with isotonic sodium chloride solution to restore extracellular fluid volume that may be depleted secondary to vomiting and to induce calciuresis. Consider the addition of loop diuretics (eg, furosemide) only after normal hydration is restored. In extreme cases, either hemodialysis or peritoneal dialysis with low or zero calcium dialysate could be used. Although not routinely used in pediatrics, newer studies are demonstrating that the bisphosphonates (antiresorptive agents) can be safely used in children and may lower serum calcium levels by decreasing bone resorption. Also, mobilization should be encouraged to prevent the hypercalcemia that occurs secondary to bed rest.
Recently published is the first-known successful case of combined treatment with bisphosphonates and a calcimimetic to treat neonatal severe hyperparathyroidism. Caution must be advised, however, inasmuch as there are no series of patients with this condition successfully treated with the aforementioned combination.
For primary hyperparathyroidism, subtotal or total parathyroidectomy is the most common choice for adults or children, depending on the number of glands involved with tumors. Parathyroidectomy can result in reference range serum calcium levels, an increase in bone mineral density, and successful prevention of kidney stones. Also, in patients with uremia, subtotal or total parathyroidectomy is an option when medical management with calcitriol or one of its analogs is unsuccessful or when tertiary hyperparathyroidism that is independent of external feedback develops.
Postoperative complications include transient hypocalcemia because parathyroids regain their sensitivity to circulating calcium. Hungry bone syndrome, a prolonged period of hypocalcemia, can occur postoperatively in those cases of primary hyperparathyroidism that demonstrated significant bone demineralization. Bones reaccumulate calcium at the expense of circulating levels. Finally, as in thyroid surgery, a risk of damage to the recurrent laryngeal nerve resulting in permanent hoarseness of the voice is observed.
The primary care provider should consult an adult or pediatric endocrinologist. Also, a radiologist should be consulted if the condition may involve the bones. Consultation with a surgeon may be obtained after consultation with the pediatric endocrinologist. Consult an oncologist if malignancy underlies hypercalcemia. Consult a nephrologist, a urologist, or both, if chronic renal failure is causing secondary hyperparathyroidism or if renal calculi develop. Genetic counseling for the patient and family members should be offered if the diagnosis of multiple endocrine neoplasia (MEN) is made.
No strict dietary requirements are necessary for management of primary hyperparathyroidism.
For secondary hyperparathyroidism, dietary management depends on the underlying disease state. For renal disease, phosphate may be restricted depending on the success of dialysis treatment or oral phosphate–binding therapy. For liver disease or malabsorptive syndromes, oral or intravenous supplementation of calcium, phosphate, magnesium, and vitamin D are helpful in minimizing the inadequacy of these nutrients caused by malabsorption or other loss.
Restrictions are mandated according to the underlying chronic disease.
Kifor O, Moore FD Jr, Wang P. Reduced immunostaining for the extracellular Ca2+-sensing receptor in primary and uremic secondary hyperparathyroidism. J Clin Endocrinol Metab. 1996 Apr. 81(4):1598-606. [Medline].
Silverberg SJ, Bilezikian JP. Primary Hyperparathyroidism. Rosen CJ. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. Seventh. Washington DC: American Society for Bone and Mineral Research; 2008. 302-6.
McMullen T, Bodie G, Gill A, et al. Hyperparathyroidism after irradiation for childhood malignancy. Int J Radiat Oncol Biol Phys. 2009 Mar 15. 73(4):1164-8. [Medline].
Al-Khalaf FA, Ismail A, Soliman AT, Cole DE, Ben-Omran T. Neonatal severe hyperparathyroidism: further clinical and molecular delineation. Eur J Pediatr. 2011 May. 170(5):625-31. [Medline].
Burke JF, Chen H, Gosain A. Parathyroid conditions in childhood. Semin Pediatr Surg. 2014 Apr. 23(2):66-70. [Medline].
Romero Arenas MA, Morris LF, Rich TA, et al. Preoperative multiple endocrine neoplasia type 1 diagnosis improves the surgical outcomes of pediatric patients with primary hyperparathyroidism. J Pediatr Surg. 2014 Apr. 49(4):546-50. [Medline].
Richert L, Trombetti A, Herrmann FR, et al. Age and gender distribution of primary hyperparathyroidism and incidence of surgical treatment in a European country with a particularly high life expectancy. Swiss Med Wkly. July 2009. 11:400-4. [Medline].
Libansky P, Astl J, Adamek S, et al. Surgical treatment of primary hyperparathyroidism in children: Report of 10 cases. Int J Pediatr Otorhinolaryngol. 2008 Aug. 72(8):1177-82. [Medline].
Garcia-Garcia E, Dominguez-Pascual I, Requena-Diaz M, et al. Intraoperative parathyroid hormone monitoring in neonatal severe primary hyperparathyroidism. Pediatrics. 2014 Oct. 134(4):e1203-5. [Medline].
Khosla S, Melton III LJ, Wermers RA. Primary hyperparathyroidism and the risk of fractures: A population-based study. J Bone Miner Res. 1999. 14:1700-1707. [Medline].
Sneider MS, Solorzano CC, Montano RE, Anello C, Irvin GL 3rd, Lew JI. Sporadic primary hyperparathyroidism in young individuals: different disease and treatment?. J Surg Res. 2009. 155:100-3. [Medline].
Silverberg SJ, Shane E, Jacobs TP. A 10-year prospective study of primary hyperparathyroidism with or without parathyroid surgery. N Engl J Med. 1999. 341:1249-1255. [Medline].
Benaderet AD, Burton AM, Clifton-Bligh R, Ashraf AP. Primary hyperparathyroidism with low intact PTH levels in a 14-year-old girl. J Clin Endocrinol Metab. 2011 Aug. 96(8):2325-9. [Medline]. [Full Text].
Muscheites J, Wigger M, Drueckler E, Fischer DC, Kundt G, Haffner D. Cinacalcet for secondary hyperparathyroidism in children with end-stage renal disease. Pediatr Nephrol. 2008 May 27. [Medline].
Wilhelm-Bals A, Parvex P, Magdelaine C, Girardin E. Successful use of bisphosphonate and calcimimetic in neonatal severe primary hyperparathyroidism. Pediatrics. 2012 Mar. 129(3):e812-6. [Medline].
Sanchez CP. Secondary hyperparathyroidism in children with chronic renal failure: pathogenesis and treatment. Paediatr Drugs. 2003. 5(11):763-76. [Medline].
Seeherunvong W, Nwobi O, Abitbol CL, Chandar J, Strauss J, Zilleruelo G. Paricalcitol versus calcitriol treatment for hyperparathyroidism in pediatric hemodialysis patients. Pediatr Nephrol. 2006 Oct. 21(10):1434-9. [Medline].
Arnold A. Familiar hyperparathyroid syndromes. Favus MJ. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. Sixth. Washington DC: American Society for Bone and Mineral Research; 2006. 185-188.
Aubin JE, Lian JB, Stein GS. Bone Formation: Maturation and Functional Activities of Osteoblast Lineage Cells. Favus MJ. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. Sixth. Washington DC: American Society for Bone and Mineral Research; 2006. 20-29.
Bilezekian JP, Silverberg SJ. Primary Hyperparathyroidism. Favus MJ. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. Sixth. Washington DC: American Society for Bone and Mineral Research; 2006. 181-185.
Hebert SC. Therapeutic use of calcimimetics. Annu Rev Med. 2006. 57:349-64. [Medline].
Langman CB. Hypercalcemic Syndromes in Infants and Children. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. Sixth. Washington DC: American Society for Bone and Mineral Research; 2006. 209-212.
Martin KJ, Al-Aly Z, Gonzalez EAl. Renal Osteodystrophy. Favus MJ. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. Sixth. Washington DC: American Society for Bone and Mineral Research; 2006. 359-366.
Marx SJ. Familial Hypocalciuric Hypercalcemia. Familial hypocalciuric hypercalcemia. In: Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. Sixth. Washington DC: American Society for Bone and Mineral Research; 2006. 188-190.
Morony S, Capparelli C, Lee R. A chimeric form of osteoprotegerin inhibits hypercalcemia and bone resorption induced by IL-1 beta, TNF-alpha, PTH, PTHrP, and 1,25 (OH)2D3. J Bone Miner Res. 1999. 14:1478-1485. [Medline].
National Kidney Foundation. Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease. Am J Kid Dis. 2003. 42 suppl 3:S1-202.
Ross FP. Osteoclast Biology and Bone Resorption. Favus MJ. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. Sixth. Washington DC: American Society for Bone and Mineral Research; 2006. 30-35.
United States Pharmacopeia. Vitamin D and Analogs Systemic. USP Dispensing Information: Advice to the Health Care Professional. 2004. 1:2849-57.
Vestergaard P, Nielsen LR, Mosekilde L. [Cinacalcet--a new drug for the treatment of secondary hyperparathyroidism in patients with uraemia, parathyroid cancer or primary hyperparathyroidism]. Ugeskr Laeger. 2006 Jan 3. 168(1):29-32. [Medline].
Wada M, Nagano N, Nemeth EF. The calcium receptor and calcimimetics. Curr Opin Nephrol Hypertens. 1999. 8:429-433. [Medline].