eMedicine Specialties > Pediatrics: General Medicine > Endocrinology
Hyperparathyroidism: Treatment & Medication
Updated: Aug 13, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
Medical management of primary hyperparathyroidism has not been satisfactory because no agents are available that can produce either sustained blockage of PTH release by parathyroid glands or sustained blockage of hypercalcemia. However, research is currently underway to develop calcimimetics, which can stimulate up-regulation 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.4 In addition, human osteoprotegerins, which can block PTH-induced hypercalcemia, are also undergoing clinical studies.
For secondary hyperparathyroidism that occurs with chronic renal failure, parenteral administration of calcitriol is helpful; however, this manner of administration is feasible only for those 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, that can treat secondary hyperparathyroidism without raising serum calcium and phosphorus levels.
For those 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.
Surgical Care
- Parathyroidectomy
- 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.
- Surgical complications
- 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.
Consultations
- 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 MEN is made.
Diet
- 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 would be helpful to minimize inadequacy of these nutrients caused by malabsorption or other loss.
Activity
Restrictions are mandated according to the underlying chronic disease.
Medication
At present, satisfactory medical therapy for primary hyperparathyroidism is being developed and early studies are promising. Pharmacologic treatment for secondary hyperparathyroidism is currently oral or parenteral calcitriol (1,25-dihydroxyvitamin D) in patients with renal failure. However, increasing use of paricalcitol or cinacalcet may reduce the need for surgical resection.
Vitamin D analogs
These agents regulate serum calcium levels via actions on calcium and phosphorus metabolism at intestinal, renal, and skeletal sites. The kidney appears to play a central role in this system. It produces calcitriol (ie, 1,25-dihydroxyvitamin D, the primary active metabolite of vitamin D3), which acts on distal organs, and at the same time is the target organ for PTH, calcitonin, and possibly calcitriol. Calcitriol is administered to help suppress excessive PTH release and blunt the hyperparathyroid response to chronic renal failure.
Unlike calcitriol, a new vitamin D analog, paricalcitol, can treat secondary hyperparathyroidism without raising serum calcium and phosphorus levels. Paricalcitol is not yet extensively used in pediatric patients, but articles by Sanchez5 and Seeherunvong et al6 have described initial data suggesting safety and effectiveness in children.
Calcitriol (Calcijex, Rocaltrol)
Used in attempted suppression of PTH secretion stimulated by inability of the kidneys to excrete phosphate, with its consequent accumulation in blood. Increases calcium levels by promoting absorption of calcium in the intestines and retention in the kidneys. Has not been tried in patients with other causes of secondary hyperparathyroidism.
Adult
Peritoneal dialysis: 0.5-5 mcg/dose PO 2-3 times/wk
Hemodialysis: 1-2 mcg/dose IV 2-3 times/wk
Pediatric
0.01-0.04 mcg/kg/d PO
IV dose is not established; not to exceed adult dose
Cholestyramine and colestipol decrease absorption of calcitriol; magnesium-containing antacids and thiazide diuretics can increase calcitriol effects
Documented hypersensitivity; hypercalcemia; malabsorption syndrome; hypervitaminosis D; renal osteodystrophy with hyperphosphatemia
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Maternal hypersensitivity to vitamin D during pregnancy may lead to Williams syndrome; growth arrest may result in children fed ergocalciferol 1800 U/d; major precaution involves monitoring to avoid hypercalcemia
Paricalcitol (Zemplar)
For treatment of secondary hyperparathyroidism in ESRD. Reduces PTH levels, stimulates calcium and phosphorous absorption, and stimulates bone mineralization.
Adult
0.04-0.1 mcg/kg IV bolus 3 times/wk; adjust dose based on PTH levels
Pediatric
<5 years: Not established
5-19 years: Data limited, 0.04-0.08 mcg/kg IV 3 times/wk; adjust dose based on PTH levels
Do not use phosphate or vitamin D-related compounds concomitantly with paricalcitol; caution if administered with digoxin (digitalis toxicity is potentiated by hypercalcemia)
Documented hypersensitivity; hypercalcemia; vitamin D toxicity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in breastfeeding; adverse effects include GI tract distress, dry mouth, lightheadedness, edema, chills, or fever
Isotonic crystalloids
Sodium chloride 0.9% fluid is used to supply intravenous hydration to replace fluids lost by emesis for patients with acute hypercalcemia of any etiology.
Sodium chloride 0.9%, IV (Normal saline)
Commonly used solution that is designed to replace circulating crystalloid lost by emesis.
Adult
Dosage depends on the estimated fluid loss; in patients with normal renal function, continuous IV infusion over 24-48h usually lowers serum Ca by 1-3 mg/dL
Pediatric
20-40 mL/kg IV over the first h in patients with normal renal function
Depending on the degree of dehydration, use sufficient isotonic sodium chloride solution to replace 50% of the deficit over the first 8 h and the remainder of the deficit over the next 16 h
May decrease levels of lithium when administered concurrently
Fluid retention; hypernatremia; acute renal failure or chronic renal disease; inappropriate ADH secretion
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in congestive heart failure, hypertension, edema, liver cirrhosis, renal insufficiency, and sodium toxicity
Loop diuretics
Once hydration has been established, use of a diuretic (eg, furosemide) can help increase calciuresis without adding to the dehydration caused by hypercalcemia.
Furosemide (Lasix)
Increases excretion of water by interfering with chloride-binding cotransport system, which in turn inhibits sodium and chloride reabsorption in the ascending loop of Henle and the distal renal tubule.
The published doses of 80-100 mg for adults and 25-50 mg for children IV q4h should be reserved for the most severe cases.
Adult
10-20 mg IV q2-4h prn for acute hypercalcemia
Pediatric
1 mg/kg IV; may cautiously increase dose by 1 mg/kg q2h; not to exceed 6 mg/kg/dose
Metformin decreases furosemide concentrations; furosemide interferes with hypoglycemic effect of antidiabetic agents and antagonizes muscle-relaxing effect of tubocurarine; auditory toxicity appears to be increased with coadministration of aminoglycosides and furosemide; hearing loss of varying degrees may occur; anticoagulant activity of warfarin may be enhanced when taken concurrently with this medication; increased plasma lithium levels and toxicity are possible when taken concurrently with this medication
Documented hypersensitivity; hepatic coma; anuria; state of severe electrolyte depletion
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Neonates exhibit a prolonged half-life (consider extending dosage interval); measure serum electrolytes, CO2, glucose, creatinine, uric acid, calcium, and BUN levels
Bisphosphonates
Bisphosphonates are antiresorptive agents that are used to help preserve bone mass. They are available in oral and parenteral forms. The inhibition of bone resorption produces a hypocalcemic effect. These agents are used in the management of conditions associated with increased bone resorption (eg, osteoporosis, Paget disease, management of hypercalcemia [especially that associated with malignancy]).
In case of acute hypercalcemia with vomiting, parenteral therapy is recommended. By reducing bone resorption, a calcium-lowering effect in the blood may occur.
Pamidronate (Aredia)
IV bisphosphonate that acts as an antiresorptive agent. Inhibits normal and abnormal bone resorption. Appears to inhibit bone resorption without inhibiting bone formation and mineralization. Currently accepted uses include the treatment of hypercalcemia associated with neoplasms and metastases as well as for treatment of Paget disease. This category of drugs is not approved for the treatment of hypercalcemia secondary to hyperparathyroidism; however, in practice, can be used for this as well as in the management of postmenopausal osteoporosis. Now being used in pediatrics to treat osteogenesis imperfecta and idiopathic juvenile osteoporosis. Preliminary study results on its use to prevent bone loss following severe burns appear promising.
Adult
60-90 mg IV infused over 8 h; prepare IV by mixing in 1 L of dextrose 5% and water solution
Pediatric
Not established; some studies have used 1.5 mg/kg/dose IV infused over 12 h; not to exceed 90 mg/dose; prepare IV by mixing 1 L of dextrose 5% and water
None reported
Documented hypersensitivity; hypocalcemia
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Monitor hypercalcemia-related parameters, such as serum levels of calcium, phosphate, magnesium, and potassium once treatment begins; adequate intake of calcium and vitamin D is necessary to prevent severe hypocalcemia; caution when administering bisphosphonates in patients with active upper GI problems (eg, gastric irritation, nausea, GI pain)
Calcimimetic Agent
These agents reduce PTH levels. A small clinical trial by Muscheites et al in children showed an 80% decrease in serum PTH levels.4
Cinacalcet (Sensipar)
Directly lowers intact parathyroid hormone (iPTH) levels by increasing sensitivity of calcium sensing receptor on chief cell of parathyroid gland to extracellular calcium. Also results in concomitant serum calcium decrease. Indicated for secondary hyperparathyroidism in patients with chronic kidney disease on dialysis.
Adult
30 mg PO qd initially; slowly titrate upward (no more frequent than q2-4wk intervals) by 30 mg increments to target iPTH of 150-300 pg/mL
Take with meals or immediately following; do not crush, chew or cut tab
Pediatric
Not established, but note that 0.25 mg/kg PO qd for 4 wk has been shown to be effective in lowering circulating PTH levels
Strong CYP450 2D6 inhibitor; may increase serum levels of CYP 2D6 substrates (eg, flecainide, vinblastine, thioridazine, tricyclic antidepressants); coadministration with CYP450 3A4 inhibitors (eg, ketoconazole, erythromycin, itraconazole) may decrease cinacalcet clearance
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Serum calcium reduction may cause lowered seizure threshold, paresthesia, myalgia, cramping, and tetany; monitor calcium and phosphorus levels closely within 1 wk following initial dose or dose changes, and then monthly (secondary hyperparathyroidism) and q2 mo (parathyroid carcinoma); do not initiate treatment if serum calcium below 8.4 mg/dL; adynamic bone disease may occur if iPTH levels suppressed below 100 pg/mL; caution with hepatic impairment; common adverse effects include nausea and vomiting
More on Hyperparathyroidism |
| Overview: Hyperparathyroidism |
| Differential Diagnoses & Workup: Hyperparathyroidism |
 Treatment & Medication: Hyperparathyroidism |
| Follow-up: Hyperparathyroidism |
| References |
| « Previous Page | Next Page » |
References
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. Apr 1996;81(4):1598-606. [Medline].
Libansky P, Astl J, Adamek S, et al. Surgical treatment of primary hyperparathyroidism in children: Report of 10 cases. Int J Pediatr Otorhinolaryngol. Aug 2008;72(8):1177-82. [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].
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. May 27 2008;[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. Oct 2006;21(10):1434-9. [Medline].
Arnold A. Familiar hyperparathyroid syndromes. In: 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. In: 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. In: 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. In: 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. In: 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. In: 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. In: 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.
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].
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. Jan 3 2006;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].
Further Reading
Keywords
hyperparathyroidism, primary hyperparathyroidism, secondary hyperparathyroidism, tertiary hyperparathyroidism, parathyroid adenoma, parathyroid hyperplasia, hypocalcemia, intestinal malabsorption, chronic renal failure, multiple endocrine neoplasia, MEN, nutritional rickets, hypercalcemia, bradycardia, dehydration, jaw tumors, Wilms tumor, fractures, Zollinger-Ellison tumors, pancreatitis, urolithiasis, nephrolithiasis, nephrocalcinosis, bone resorption, vitamin D malabsorption, cholestatic liver disease, Paget disease
