AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

The parathyroid glands regulate serum calcium and phosphorus levels through the secretion of parathyroid hormone (PTH), which raises serum calcium levels while lowering the serum phosphorus concentration. The regulation of PTH secretion occurs through a negative feedback loop in which calcium-sensing receptors on the membranes of parathyroid cells trigger decreased PTH production as serum calcium concentrations rise.

Primary hyperparathyroidism, which accounts for most hyperparathyroidism cases, results from excessive release of PTH and manifests as hypercalcemia.¹ Patients with hypercalcemia who have normal renal function and no malignancy must be suspected of having primary hyperparathyroidism and must be subsequently tested for elevated PTH levels.

Hyperparathyroidism is often incidentally discovered during routine laboratory testing when hypercalcemia is noted. In 80% of patients with hyperparathyroidism, the symptoms of hypercalcemia are mild or are not notable at the time of discovery. Management of these patients is not clear-cut because routine laboratory tests have not been shown to assist in predicting development of overt manifestations of the disease. Conversely, patients with overtly symptomatic hyperparathyroidism (eg, those with urinary tract stones, bone pain, cognitive abnormalities) and those with marked hypercalcemia (calcium levels >10.2 mg/dL) must be referred for parathyroidectomy.²

Pathophysiology

Primary hyperparathyroidism is one of the most common causes of hypercalcemia and should be considered in any individual with an elevated calcium level.³ Primary hyperparathyroidism is usually the result of a single benign adenoma; a minority of patients have hyperplasia in all 4 parathyroid glands. Parathyroid carcinoma accounts for an insignificant minority (<0.5% of patients with hyperparathyroidism).

Asymptomatic primary hyperparathyroidism manifests with serum calcium concentrations only slightly elevated to within 1 mg/dL above the upper limit of the reference range. Within the setting of asymptomatic primary hyperparathyroidism, the PTH level is typically 1.5-2 times the upper limit of the reference range. Hypophosphatemia and hyperchloremia are typically seen only in patients who are highly symptomatic patients and have advanced hyperparathyroidism.

When hyperparathyroidism manifests with hyperplasia in all 4 glands, familial-genetic syndromes should be considered within the differential diagnosis. Syndromes to be considered include type I and type II multiple endocrine neoplasia (MEN) or, less commonly, familial hypocalciuric hypercalcemia and hyperparathyroidism–jaw tumor syndrome. Also, a syndrome of familial isolated hyperparathyroidism has been observed. Radiation therapy to the head and neck predisposes subjects to parathyroid tumors.

Secondary hyperparathyroidism occurs when the parathyroid glands become hyperplastic after long-term hyperstimulation and release of PTH. In secondary hyperparathyroidism, elevated PTH levels do not result in hypercalcemia. This has been classically attributed to an underlying state of hypocalcemia in those with chronic renal failure (CRF). However, hypocalcemia is not necessary for the development of secondary hyperparathyroidism in this setting. Additional risk factors for the development of secondary hyperparathyroidism include phosphorus retention, intrinsic parathyroid gland abnormalities, diminished serum calcitriol levels, and resistance to PTH by skeletal tissue. Rickets and malabsorption syndromes are rarer causes.

With long-term hyperstimulation, the glands function autonomously and produce high levels of PTH even after correction of chronic hypocalcemia. Tertiary hyperparathyroidism refers to hypercalcemia caused by autonomous parathyroid function after long-term hyperstimulation.

Frequency

United States

Primary hyperparathyroidism is a common endocrine disease that affects nearly 1 in 500 women and 1 in 2000 men per year, most often in the fifth, sixth, and seventh decades of life.⁴

Mortality/Morbidity

Most patients, who are predominantly elderly, present with mild elevations of serum calcium and are not overtly symptomatic. Usually, the rate of progression of hyperparathyroidism is slow, and monitoring these patients and medically managing the disease is usually safe.

Although operative mortality is low, no evidence suggests that primary hyperparathyroidism with mild hypercalcemia has an adverse effect on survival.³ Conversely, parathyroidectomy remains the appropriate therapy for symptomatic or complicated primary hyperparathyroidism. Complication rates and symptom relief are the same in younger and older patients who undergo surgery.³

Sex

Most individuals with hyperparathyroidism are older women.³

Age

Although hyperparathyroidism can arise at any age, its occurrence rises markedly after age 40 years. Hyperparathyroidism is rare in children.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Most patients with primary hyperparathyroidism are asymptomatic or minimally symptomatic. Because manifestations of hyperparathyroidism are subtle, the disease may run a benign course for years prior to detection. Symptomatic hyperparathyroidism is characterized by vague, nonspecific symptoms including generalized weakness, fatigue, poor concentration, and depression.

Nephrolithiasis that results in ureteral colic is secondary to serum calcium elevations. As many as 75% of patients who undergo surgical treatment for primary hyperparathyroidism present with nephrolithiasis. Furthermore, patients with primary hyperparathyroidism not only have a greater risk of renal stone disease, but this risk persists for 10 years after surgery.⁵ Overt bone disease, including subperiosteal bone resorption and osteitis fibrosa cystica, is a serious but rare manifestation of hyperparathyroidism. Proximal muscle weakness may occur, typically affecting the lower limbs more than the upper limbs. Chondrocalcinosis and pseudogout are other potential complications of hyperparathyroidism.

Rarely, hyperparathyroidism may abruptly worsen and may cause severe hypercalcemic complications such as profound dehydration, altered mental status, or coma. This is referred to as hypercalcemic parathyroid crisis.

• A helpful mnemonic, "painful bones, renal stones, abdominal groans, and psychic moans," can be used to recall the typical symptoms of hypercalcemia. Painful bones are the result of abnormal bone remodeling due to overproduction of parathyroid hormone (PTH). Nephrolithiasis occurs secondary to hyperparathyroid disease–induced hypercalcemia and resultant hypercalciuria. Abdominal groans refers to hypercalcemia-induced ileus. Psychic moans or depression may occur in the presence of persistently elevated serum calcium levels.
• The most frequent complication of primary hyperparathyroidism is nephrolithiasis, which occurs in about 20% of patients.⁴ Renal effects of the disease also include decreased glomerular filtration rate. Hypercalciuria (>300 mg daily calcium excretion) is observed in a significant subset of patients (£30%).
• Some patients suffer from easy fatigability, a sense of generalized weakness, or mild cognitive impairment.

Physical

No highly specific physical findings are present in hyperparathyroidism.

• CNS
• • Neuropsychiatric illness
  • Altered mental status
  • Coma (severe cases)
• Cardiovascular system
• • Signs of hypertension and congestive heart failure may be apparent, although little definitive evidence supports a causal relationship.
  • The association of primary hyperparathyroidism with hypertension has been well documented but remains poorly understood. Whether parathyroidectomy alters the long-term course of hypertension is unclear because surgery does not reliably result in improvement.³
• Musculoskeletal system
• • Osteoporosis
  • Osteopenia
  • Cystic bone lesions
  • Vertebral collapse
  • Chondrocalcinosis and pseudogout
  • Easily fatigued muscle (particularly proximal muscle groups)
• GI system
• • Pancreatitis, pancreatic calcification, or both
  • Peptic ulcer disease (may be present at a higher rate)
• Renal system: The renal manifestations of primary hyperparathyroidism include recurrent calcium nephrolithiasis, nephrocalcinosis, and impaired renal function.⁵

Causes

• A single parathyroid adenoma is the underlying pathology in 85% of cases.
• Diffuse hyperplasia of all parathyroid glands occurs in approximately 15% of cases. More than half of these are part of a familial syndrome.
• Parathyroid carcinoma is a very rare cause of primary hyperparathyroidism.
• Secondary hyperparathyroidism occurs when the parathyroid glands are chronically stimulated to release PTH.
• • Chronic renal failure
  • Malabsorption syndromes
  • Rickets
• Long-standing secondary hyperparathyroidism may progress into autonomous hypersecretion of PTH even after correction of chronic hypocalcemia; it is termed tertiary hyperparathyroidism.
• External radiation to the head, neck, and chest regions is associated with an increased likelihood of developing benign parathyroid tumors. Parathyroid adenomas reported after radiation exposure are usually hyperfunctioning and are usually detected upon manifestations of primary hyperparathyroidism.⁶ Patients with radiation-induced hyperparathyroidism are also more likely to have coexistent nodular goiter and thyroid gland carcinoma than patients with spontaneous hyperparathyroidism.⁷

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Adverse drug reaction to lithium
Adverse reaction to parenteral nutrition
Adverse drug reaction to thiazide diuretics
Cancers producing parathyroid hormone–related protein
Cancers producing ectopic production of 1,25-dihydroxyvitamin D
Familial hypocalciuric hypercalcemia
Berylliosis
Histoplasmosis
Coccidioidomycosis
Immobilization
Leprosy
Lytic bone metastasis
Milk-alkali syndrome
Multiple endocrine neoplasms
Pheochromocytoma
Vasoactive intestinal polypeptide hormone–producing tumor
Ectopic hyperparathyroidism
Exogenous calcium intake
Sarcoidosis

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Elevated parathyroid hormone (PTH) levels in the setting of hypercalcemia establish the diagnosis of hyperparathyroidism. The most common other cause of hypercalcemia in older individuals, hypercalcemia of malignancy, is associated with suppressed PTH levels.
• Although measuring the concentration of ionized calcium rather than the total calcium concentration provides added accuracy, one may alternatively use the total serum calcium concentration corrected for the patient's albumin concentration. This can be achieved by adding 0.8 per dL to the total serum calcium value for every 1 g/dL below a serum albumin concentration of 4 g/dL. Those with secondary hyperparathyroidism and associated chronic renal failure are especially prone to hypoalbuminemia, thus, this correction is of particular importance.
• The normal range for the PTH-intact assay is generally 10-65 pg/mL.
• A decreased serum phosphate level of less than 2.5 mg/dL (0.81 mmol/L) may be seen.
• Increased bone turnover may be reflected in elevated levels of markers of bone formation (alkaline phosphatase) and bone resorption (urinary pyridinoline).
• Urinary calcium excretion may be elevated.
• A newly introduced immunoradiometric assay for PTH detects only the fully intact molecule and, as such, may be more accurate than the most commonly used assay that measures truncated, nonfunctional molecules along with the full-length molecule.
• Expedited determination of PTH levels in the intraoperative setting with rapid laboratory assays has been used during parathyroid excisions. Because of the short half-life of PTH (<5 min), intraoperative measurement is recommended by the National Academy of Clinical Biochemistry Guidelines.⁸ The commercially available rapid PTH assay provides an accurate PTH level that can be used intraoperatively to determine quantitatively when all hyperfunctioning parathyroid tissue has been excised. A decrease in the PTH concentration of more than 50% from the baseline level 5-10 minutes after excision of all suspected hyperfunctioning parathyroid tissue suggests the absence of any residual hyperfunctioning tissue. 
• The advent of intraoperative PTH testing has reduced the postoperative failure rate of initial parathyroidectomy surgery from 6% to 1.5%⁹ and has decreased the need for performing frozen sections.¹⁰

Imaging Studies

The noninvasive imaging modalities commonly used in patients with primary hyperparathyroidism include technetium-99m (^99mTc) sestamibi imaging, ultrasonography, CT scanning, and MRI. 

• Ultrasonography and ^99mTc sestamibi scanning have the advantages of being widely available and relatively inexpensive compared with other noninvasive modalities. 
• • The most sensitive and reliable technique is ^99mTc sestamibi tomographic reprojection nuclear scanning because of its ability to produce a 3-dimensional image that can be used for visual reference by the surgeon intraoperatively.¹¹
  • In sestamibi scanning, the dual isotope technique in which an I-123NaI or ^99mTc sestamibi image of the thyroid is subtracted from a ^99mTc sestamibi image is commonly used.¹² 
  • Sestamibi scintigraphy has the advantage of being able to screen the entire mediastinal and cervical regions.
  • High-resolution real-time cervical ultrasonography using a 10-MHz transducer results in true positive findings in 50-60% of patients who undergo evaluation for persistent or recurrent primary hyperparathyroidism. 
  • Using ultrasonography, hyperfunctioning parathyroid tissue has a characteristic sonolucent signal that is distinct from thyroid. 
  • The best ultrasonography results reveal parathyroid tissue in one of the normal cervical locations adjacent to the thyroid gland.¹²
  • Ultrasonography may be useful but is also operator-dependent.¹¹
• Radiography has limited diagnostic value, especially in the early stages of the disease. Normal radiography findings do not rule out hyperparathyroidism. Radiography findings are uncommon and are associated with overt, symptomatic disease. Abnormal radiography findings include subperiosteal resorption that is best seen at the radial sides of the phalanges, distal phalangeal tufts, and distal clavicles. However, in most older patients, no specific radiologic manifestations are observed, and skeletal radiography is not recommended.
• Bone-density measurements based on dual energy x-ray absorptiometry (DXA) at the hip and spine should be obtained in individuals with primary hyperthyroidism, regardless of age.³
• Cystic bone lesions called brown tumors are seen only in patients who are severely affected. Soft tissue calcification may be apparent in the joints, kidneys, and lungs using conventional radiography and may be more readily evident on bone scans.
• CT scanning of the spine provides reproducible quantitative estimates of spinal bone density. Serial measurements can provide an early indication of whether or not progressive osteopenia is present.

Other Tests

• Several techniques are available for preoperative localization of hypersecreting parathyroid glands.

Procedures

• If malignancy is suspected, percutaneous needle biopsy may be performed for aspiration cytology and tissue PTH determination.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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. 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 with profound hypercalcemia presenting with severe alterations of mental status, loop diuretics facilitate the urinary excretion of calcium and can prevent the volume overload that may accompany the administration of large volumes of saline. 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,¹³ bone mineral density in the femoral neck rises by 6% after 1 year and rises by 14% after 10 years.¹¹
• 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:¹⁴
• • 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 patients must have serum calcium levels periodically monitored.¹¹
• 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.¹¹

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%.¹¹

• 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.¹¹
• 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.¹¹
• 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

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Intravenous hydration with isotonic sodium chloride solution adequately reduces calcium levels in most patients with hyperparathyroid-induced hypercalcemia.

In patients who are postmenopausal and who do not undergo surgery, estrogen may be beneficial to help maintain bone mass. However, a 1991 National Institutes of Health Consensus Conference on Management of Asymptomatic Hyperparathyroidism did not recommend estrogen therapy, citing insufficient cumulative experience to warrant a recommendation.¹⁵

The use of other calcium-lowering agents, such as bisphosphonates, plicamycin, and calcitonin, are used to treat oncologic causes of hypercalcemia and are not used for hyperparathyroidism.

Cinacalcet, a calcimimetic drug that reduces parathyroid hormone (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 one week to allow dose adjustment.

Drug Category: Loop diuretics

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

Drug Category: Hormonal therapy

Hormone therapy is indicated in postmenopausal females with hyperparathyroidism.

Drug Category: 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.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Admit patients with significant symptoms due to hyperparathyroid-induced hypercalcemia and substantial elevations of calcium levels.
• Patients who are markedly symptomatic or those with significant electrolyte disturbances should be evaluated by endocrinologists and surgeons experienced in parathyroid removal.

Further Outpatient Care

• Calcium levels must be periodically monitored for several months postparathyroidectomy.
• If calcium levels begin to rise postoperatively, the patient needs to be evaluated for possible accessory parathyroid glands.
• Monitor asymptomatic patients for worsening hypercalcemia, deteriorating bone density or renal function, and other complications of hyperparathyroidism.
• If the serum calcium concentration falls below 8 mg/dL postparathyroidectomy with a concomitant rise in serum phosphate level, consider the possibility of postsurgical hypoparathyroidism.

Deterrence/Prevention

• Although patients should refrain from the ingestion of more calcium than is recommended for adults (1200-1500 mg/d), the calcium intake should not be excessively restricted (to <750 mg/d) because calcium-poor diets may promote processes associated with excessive secretion of parathyroid hormone (PTH).
• Because many patients with asymptomatic primary hyperparathyroidism have levels of 25-hydroxyvitamin D that are at the lower end of the reference range or frankly low, the addition of a low level of supplementation achievable with a multivitamin (400 IU of vitamin D daily) is advisable.

Complications

• Maternal hyperparathyroidism can lead to profound hypocalcemia and tetany, coma, and death in newborns in a syndrome known as neonatal severe hyperparathyroidism.
• Nocturia and polyuria may result from the effects of elevated calcium levels on the renal tubule.
• Approximately 20% of patients with hyperparathyroidism have nephrolithiasis.
• CNS disturbances, coma, and death may result from markedly elevated serum calcium levels when left untreated.
• Skeletal sequelae (eg, pathologic fracture) may occur.
• Heart failure may occur.
• Surgical complications include the following:
• • Hypoparathyroidism
  • Recurrent laryngeal nerve damage
  • Hemorrhage
  • Infection
  • Unsuccessful surgery
  • • Persistent or recurrent disease occurs in 5-10% of individuals who undergo surgery for primary hyperparathyroidism.¹² 
    • Persistent primary hyperparathyroidism is defined as the presence of elevated serum calcium levels and PTH levels documented within 6 months of the initial operation. The most common cause of persistent primary hyperparathyroidism is the presence of a missed parathyroid adenoma, which is usually in an ectopic location in this setting. Less commonly, persistent disease may be secondary to inadequate resection of unappreciated multigland disease.¹²

Prognosis

• The prognosis is excellent for patients after successful parathyroidectomy.
• Asymptomatic patients who do not have indications for surgery have an excellent prognosis. Significant bone loss and other symptoms may be absent for years in subsequent follow-up visits.
• Secondary hyperparathyroidism is associated with a poor prognosis likely due to underlying advanced chronic renal failure and resultant chronic hypocalcemia.

Patient Education

• Educate patients about prescribed medications.
• Educate patients regarding the importance of periodic laboratory and radiologic testing.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to address or arrange follow-up for asymptomatic patients who have mild-to-moderate elevations of calcium levels
• Failure to treat significantly elevated calcium levels, especially in symptomatic patients

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

1. Allerheiligen DA, Schoeber J, Houston RE, et al. Hyperparathyroidism. Am Fam Physician. Apr 15 1998;57(8):1795-802, 1807-8. [Medline].
2. Jacobs DS, Kasten BL, DeMott WR, Wolfson WL. Laboratory Test Handbook. Williams & Wilkins;1990:284-7.
3. Boonen S, Vanderschueren D, Pelemans W, Bouillon R. Primary hyperthyroidism: diagnosis and management in the older individual. Eur J Endocrinol. Sept 2004;151(3):297-304. [Medline].
4. Ruda JM, Hollenbeak CS, Stack BC. A systematic review of the diagnosis and treatment of primary hyperparathyroidism from 1995 to 2003. Otolaryngology- Head and Neck Surgery. March 2005;132:359-372.
5. Sorensen HA. Surgery for primary hyperparathyroidism. BMJ. Oct 12 2002;325(7368):785-6. [Medline].
6. Beard CM, Heath H 3rd, O'Fallon WM, et al. Therapeutic radiation and hyperparathyroidism. A case-control study in Rochester, Minn. Arch Intern Med. Aug 1989;149(8):1887-90. [Medline].
7. Tezelman S, Rodriguez JM, Shen W, et al. Primary hyperparathyroidism in patients who have received radiation therapy and in patients who have not received radiation therapy. J Am Coll Surg. Jan 1995;180(1):81-7. [Medline].
8. Carter AB, Howanitz PJ. Intraoperative testing for parathyroid hormone: a comprehensive review of the use of the assay and the relevant literature. Arch Pathol Lab Med. Nov 2003;127(11):1424-42. [Medline].
9. Boggs JE, Irvin GL 3rd, Carneiro DM, Molinari AS. The evolution of parathyroidectomy failures. Surgery. Dec 1999;126(6):998-1002; discussion 1002-3. [Medline].
10. Guarda LA. Rapid intraoperative parathyroid hormone testing with surgical pathology correlations: the "chemical frozen section". Am J Clin Pathol. Nov 2004;122(5):704-12. [Medline].
11. Irvin GL, Carneiro DM. Management changes in primary hyperparathyroidism. JAMA. Aug 23-30 2000;284(8):934-6. [Medline].
12. Alexander HR Jr, Chen CC, Shawker T, et al. Role of preoperative localization and intraoperative localization maneuvers including intraoperative PTH assay determination for patients with persistent or recurrent hyperparathyroidism. J Bone Miner Res. Nov 2002;17 Suppl 2:N133-40. [Medline].
13. VanderWalde LH, Liu IL, O'Connell TX, Haigh PI. The effect of parathyroidectomy on bone fracture risk in patients with primary hyperparathyroidism. Arch Surg. Sep 2006;141(9):885-9; discussion 889-91. [Medline].
14. Coker LH, Rorie K, Cantley L, et al. Primary hyperparathyroidism, cognition, and health-related quality of life. Ann Surg. Nov 2005;242(5):642-50. [Medline]. [Full Text].
15. National Institutes of Health. Consensus conference. Diagnosis and management of asymptomatic primary hyperparathyroidism. Conn Med. Jun 1991;55(6):349-54. [Medline].
16. al Zahrani A, Levine MA. Primary hyperparathyroidism. Lancet. Apr 26 1997;349(9060):1233-8. [Medline].
17. Bilezikian JP. Management of acute hypercalcemia. N Engl J Med. Apr 30 1992;326(18):1196-203. [Medline].
18. Bilezikian JP, Silverberg SJ. Clinical practice. Asymptomatic primary hyperparathyroidism. N Engl J Med. Apr 22 2004;350(17):1746-51. [Medline].
19. Potts JT. Diseases of the parathyroid gland and other hyper- and hypocalcemic disorders. In: Harrison's Principles of Internal Medicine. 14^th ed. 1998:2227-32.

Article Last Updated: May 6, 2008