eMedicine Specialties > Emergency Medicine > Endocrine & Metabolic

Hyperparathyroidism: Treatment & Medication

Author: Philip N Salen, MD, Clinical Professor, Department of Emergency Medicine, PA Program, Desales University; Adjunct Clinical Associate Professor, Department of Emergency Medicine, Temple University Medical School; Research Director, Emergency Medicine Education, Saint Luke's Hospital
Contributor Information and Disclosures

Updated: Nov 16, 2009

Treatment

Prehospital Care

Only in the most severe acute manifestation of hyperparathyroidism, hypercalcemia-induced altered mental status, does management need to begin in the prehospital setting. In such cases, prehospital care should focus on the stabilization of airway, breathing, and circulation. In the field and the emergency department, hydration is the principal primary therapy directed at hypercalcemia.

Emergency Department Care

The emergency department (ED) management of hyperparathyroidism is focused on the treatment of hypercalcemia. Specifically, the goal of treatment is to reduce the calcium level to below 11.5 mg/dL; most patients have resolution of hypercalcemia-induced symptoms when calcium levels are below this level.

• Intravenous administration of isotonic saline is the first and most vital step in the management of severe hypercalcemia.¹⁸ Severe hypercalcemia is nearly always accompanied by severe dehydration. When the depleted intravascular volume is restored to the reference range, the serum calcium concentration declines by the degree to which dehydration raised it. Subsequent hydration serves to enhance renal excretion of excess calcium.
• Hypercalcemia is mild in most asymptomatic patients with hyperparathyroidism and may be controlled with gentle hydration with normal saline.
• In patients presenting with severe alterations of mental status or other life-threatening complications from profound hypercalcemia, fluid resuscitation with normal saline, immediate institution of bisphosphonate therapy — with or without calcitonin, depending on the severity of the symptoms — is the standard of management for hypercalcemia.¹⁸
• Loop diuretics may facilitate the urinary excretion of calcium and may prevent the volume overload that may accompany the administration of large volumes of saline. However, furosemide does not consistently normalize calcium levels quickly, even at markedly higher doses than those routinely prescribed.¹⁸ Patients with hypercalcemia may be destabilized further by fluid and electrolyte disturbances caused by aggressive diuresis and, as such, should have serial chemistry panels performed for monitoring. Initiation of loop diuretics should only occur after rehydration has taken place.
• In postmenopausal women with mild hyperparathyroidism, estrogen therapy has been advocated because it may inhibit demineralization of the skeleton and may reduce blood calcium levels.
• Surgery that involves open surgical excision with frozen section diagnosis is the only definitive treatment for severe hyperparathyroidism.
• Successful parathyroidectomy induces normocalcemia in 95-98% of patients with hyperparathyroidism, and 82% of patients have symptomatic improvement. Patients with osteoporosis and hyperparathyroidism experience a prompt and sustained increase in their bone mineral density after successful parathyroidectomy.
• Although few studies related to the incidence of postparathyroidectomy fractures are available,¹⁹ bone mineral density in the femoral neck rises by 6% after 1 year and rises by 14% after 10 years.¹⁶
• Although some controversy surrounds indications for surgery, current National Institutes of Health guidelines for curative, surgical intervention indications are defined by the measurable objective criteria listed below. Approximately 20% of patients with hyperparathyroid disease meet the following criteria:²⁰
  • Patients with overt clinical manifestations of disease
  • Age younger than 50 years
  • Serum calcium concentration more than 1 mg/dL above upper limit of reference range
  • Urinary calcium excretion greater than 400 mg/d
  • Low or declining bone mineral density
  • Uncertain prospect for successful medical monitoring
  • Patient requests surgery
  • Poor or uncertain follow-up
  • Coexistent disease that may confound or contribute to disease progression
  • Reduction in creatinine clearance of 30% or more
  • Reduction of bone mineral density greater than 2.5 standard deviations below the reference range for bone density in terms of age, gender, and race (T score <2.5)
• Of note, many patients tolerate mild hyperparathyroidism well without operative treatment. Roughly 75% of asymptomatic patients who present with mild hypercalcemia did well over a 10-year period without significant loss of cortical bone, progressive hypercalcemia, or excessive urinary calcium excretion. Because no factors (other than the ones listed above) predict which patients with mild disease will experience disease progression, all asymptomatic patients, who are not operated on, must have serum calcium levels periodically monitored.¹⁶ Asymptomatic patients who were not deemed candidates for surgery had the following features: a serum calcium level less than 1 mg/dL (0.25 mmol/L) above the upper limits of normal, no history of kidney stones or fractures, a creatinine clearance that was within 30% of age- and sex-matched controls, 24-h urine calcium level less than 400 mg/24 h (0.1 mmol/kgxday), and the absence of osteoporosis by bone density T-score.⁹
• Because of the improvements in radiopharmaceutical screening and the availability of the intraoperative, rapid parathyroid hormone (PTH) assay, minimally invasive parathyroidectomies under local anesthesia are now performed; patients are discharged several hours postoperatively. This technique has altered the management and the surgical indications for hyperparathyroid in some patients. For example, symptomatic elderly patients with comorbid disease who were previously denied surgery because of risks related to anesthesia and bilateral neck dissection are now potential candidates for minimally invasive parathyroidectomy. Furthermore, in centers in which limited parathyroidectomy is available, asymptomatic patients with moderate hypercalcemia (0.4-0.9 mg/dL above normal) can be considered for earlier parathyroidectomy before severe bone loss or kidney damage occurs.¹⁶

Consultations

Surgical consultation is necessary for patients with severe hypercalcemia due to hyperparathyroidism who meet current National Institute of Health guidelines for curative surgical intervention. New techniques for identifying and operating on hyperactive parathyroid glands have improved the success rate of parathyroidectomy, as measured by a return to normocalcemia in 98% of patients, and have also simplified the operation from a bilateral neck operation under general anesthesia to a simpler outpatient procedure.

The new parathyroidectomy technique involves performing the procedure through a small incision under local anesthesia with limited, target-specific dissection. Excision of the hyperfunctioning gland is confirmed in the operating room by a quantitative decrease in the plasma PTH level, ensuring that all hypersecreting tissue has been removed. The failure rate of this minimally invasive procedure is only approximately 1.5%.¹⁶

• When normal glands are found in association with one enlarged adenomatous gland, excision of the single adenoma usually leads to a cure or eliminates symptoms.
• The surgical approach usually entails removal of a single enlarged gland; however, all glands must be examined in some way to eliminate the possibility that more than one gland is abnormal. Multiglandular disease, identified by quantitative biochemical frozen section, is present in 5% of patients with primary hyperparathyroidism and must be recognized and treated at the time of operation to ensure operative success.¹⁶
• In patients with multiple gland hyperplasia, total parathyroidectomy is performed with immediate transplantation of a portion of a removed minced parathyroid gland into the muscles of the forearm; thus, even if parathyroid gland hyperfunction recurs, surgical excision is easier from the ectopic site in the arm.
• A decline in serum calcium level occurs within 24 hours of successful surgery. Additionally, serum PTH levels fall within minutes of a successful parathyroidectomy. Intraoperative measurement of PTH can be useful in locating obscure glands through differential venous sampling, measuring increased hormone secretion after massage of specific areas, and correctly identifying the excision of abnormal parathyroid tissue when it is not easily recognized.¹⁶
• Usually, blood calcium levels fall to low reference range values for 3-5 days until the remaining parathyroid tissue resumes hormone secretion. Severe postoperative hypocalcemia is likely only if osteitis fibrosa cystica is present or if injury to all the normal parathyroid glands occurs during surgery.

Medication

Intravenous hydration with isotonic sodium chloride solution adequately reduces calcium levels in most patients with hyperparathyroid-induced hypercalcemia. Restoration of euvolemia with isotonic saline is the mainstay emergency department treatment of hypercalcemia of any cause, including primary hyperparathyroidism.

Bisphosphonate and hormone replacement therapy provide skeletal protection in patients with primary hyperparathyroidism. Neither of these classes of medications significantly lowers serum calcium or PTH levels. The magnitude of the effects of bisphosphonates and estrogen on bone mineral density in primary hyperparathyroidism is comparable to that which occurs after surgical correction of primary hyperparathyroidism.¹⁰ Of the two agents, bisphosphonates are preferred because of the adverse nonskeletal effects of long-term hormone replacement therapy.

The calcimimetic cinacalcet reduces both serum calcium and parathyroid hormone (PTH) levels and raises serum phosphorus. Cinacalcet does not, however, reduce bone turnover or improve BMD. At present, use of this agent in primary hyperparathyroidism is limited to control of serum calcium in patients with symptomatic hypercalcemia who are unable to undergo corrective surgery.¹⁰

Cinacalcet, a calcimimetic drug that reduces PTH secretion by altering the function of parathyroid calcium-sensing receptors, can be initiated in patients with hypercalcemia secondary to parathyroid carcinoma, secondary hyperparathyroidism, and primary hyperparathyroidism. For hypercalcemia from primary hyperparathyroidism or parathyroid malignancy, the starting dose is usually 30 mg orally twice daily. For those with secondary hyperparathyroidism, the starting dose is 30 mg once daily. After initiation of cinacalcet, measure the serum calcium level within 1 week to allow dose adjustment.

Loop diuretics

These agents may be helpful following hydration in individuals who are hypercalcemic.

Furosemide (Lasix)

Increases excretion of water and calcium. Interferes with chloride-binding cotransport system by inhibiting the reabsorption of sodium and chloride in the ascending loop of Henle and distal renal tubule.

Hormonal therapy

Hormone therapy is indicated in postmenopausal females with hyperparathyroidism.

Estrogen (Premarin)

Reduces bone resorption resulting from hyperparathyroidism.

Calcimimetic agents

Calcium regulators are also used in hypercalcemia of malignancy. These agents bind to and modulate the parathyroid calcium-sensing receptor, increase sensitivity to extracellular calcium, and reduce PTH secretion. Cinacalcet is a first in class calcimimetic drug that works to directly inhibit PTH in patients with CRF. Cinacalcet has been shown to significantly lower PTH and calcium levels in patients on dialysis with secondary hyperparathyroid disease ranging from mild to severe.⁴

Cinacalcet (Sensipar)

Directly lowers PTH levels by increasing sensitivity of calcium-sensing receptor on chief cell of parathyroid gland to extracellular calcium. Also results in concomitant serum calcium level decrease. Indicated for hypercalcemia with parathyroid carcinoma and for secondary hyperparathyroidism of chronic renal failure.

Bisphosphonate Derivative

Bisphosphonates are effective in decreasing bone turnover in patients with primary hyperparathyroidism and improving bone mineral density. Bisphosphonates have the potential to provide skeletal protection in patients with primary hyperparathyroidism, but the data available confirming this are limited at present. The effect on serum calcium has been inconsistent and may be affected by baseline 25-hyroxyvitamin D levels. Bisphosphonates also do not significantly lower parathyroid hormone levels.¹⁰

Alendronate

Available in the United States, but not yet indicated for treatment of hypercalcemia; alendronate probably is useful for long-term prevention of recurrence of hypercalcemia following use of more conventional therapy (ie, hydration and pamidronate). Useful in preventing and treating osteoporosis, which is a complication of prolonged mild hypercalcemia.

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