Hyperparathyroidism in Emergency Medicine Treatment & Management

Definitive therapy for symptomatic and asymptomatic PHPT is parathyroidectomy. Parathyroid induced hypercalcemic crisis is managed by volume repletion, administration of loop diuretics once the patient is euvolemic, and bisphosphonate therapy to further decrease bone resorption. ^[15]  

Only in the most severe acute manifestation of hyperparathyroidism, hypercalcemia-induced delirium, 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.

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. ^[28] 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 symptoms are 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. ^[28]

• 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. ^[28] 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.

• Parathyroidectomy 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, ^[29] bone mineral density in the femoral neck rises by 6% after 1 year and rises by 14% after 10 years. ^[27]

• 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 PHPT meet the following criteria: ^[30]

  • 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 of more 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. ^[27] 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/kg per day), and the absence of osteoporosis by bone density T-score. ^[19]

• 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. ^[27]

All patients with biochemically confirmed PHPT who have specific symptoms or signs of their disease should undergo surgical treatment. ^[23]

Surgical consultation is necessary for patients with severe hypercalcemia due to hyperparathyroidism who meet current National Institute of Health guidelines for curative surgical intervention. Surgery remains the only curative option in asymptomatic, as in symptomatic disease. ^[11]

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 low, approximately 1.5%. ^[27]

• 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. ^[27]

• 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; 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. ^[27]

• Serum ionized calcium and/or total calcium have to be monitored regularly, eg, every 6 to 12 hours for the first day post-operatively or until the patient’s calcium level is stable. ^[8]

• 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.

• To maintain the calcium levels within the normal range, many patients will need intravenous calcium substitution soon after parathyroidectomy. Oral calcium supplements can be instituted as soon as the patient is able to swallow, and the dose is progressively increased as necessary. ^[8]

In patients with asymptomatic PHPT, medical management designed to target skeletal protection or lower serum calcium might be a suitable option. It can be of value for those with contraindications to, or those who do not wish to have, surgery. Among drugs in the bisphosphonate class, alendronate in particular has been shown to decrease bone turnover and increase BMD in PHPT. Hormone replacement therapy also improved BMD in postmenopausal women with mild PHPT. It is not known whether these treatments also reduce fracture risk. ^[15]  Patients should be encouraged to engage in physical activity (to decrease bone resorption) and to maintain adequate hydration (to reduce the risk of developing serious hypercalcemia or nephrolithiasis). ^[15]

The definitive management and curative therapy for PHPT is surgery. Cure rates for surgical management of PHPT are 95% to 98%. ^[21] For an asymptomatic PHPT patient, the decision for parathyroid surgery is based upon patient characteristics including age, creatinine clearance, and bone mineral density. Specific indications for parathyroidectomy in the setting of asymptomatic PHPT are: 1. Serum calcium above upper limit of normal 0.25 mmol/L; 2. Creatinine clearance (calculated) reduced to < 60 mL/min; 3. Bone mineral density T score less than -2.5 at any site or previous fragility fracture; 4. Age less than 50 years old. ^[15]  Minimally invasive parathyroidectomy is the operative intervention of choice by the experienced endocrine surgeon if preoperative imaging localizes a parathyroid adenoma. If the parathyroid glands causing PHPT are not localized preoperatively, bilateral neck exploration is undertaken. The short half-life of PTH allows for intraoperative testing and confirmation that the abnormal gland has been excised. ^[21]

Complications from surgical management of PHPT are uncommon, 1% to 2%. ^[21]

Parathyroid hormone levels may be elevated postoperatively in as many as 20-40% of patients. If the serum calcium level remains within the reference range, this elevated state does not usually suggest persistent disease but may indicate a higher risk of recurrence. ^[31] The recurrence rate after successful parathyroidectomy is approximately 10-15% with long-term follow-up. ^[32]

Prevention

Asymptomatic PHPT patients and patients who are not undergoing surgical excision are advised to remain well hydrated, to avoid immobilization, and to avoid thiazide diuretics, which can increase serum calcium levels. There has been debate regarding the benefits of restrictions in dietary calcium intake. ^[21]

Long-term monitoring

Recommended surveillance of PHPT patients who do not undergo operative cure is measurement of: serum calcium levels twice yearly, urinary calcium excretion yearly, and bone mineral density measurements yearly. ^[21]