eMedicine Specialties > Radiology > Musculoskeletal
Hyperparathyroidism, Primary
Updated: Jan 24, 2008
Introduction
Background
In 1891, von Recklinghausen described the classic bone disease termed osteitis fibrosa cystica. In 1925, the Viennese surgeon Mandl performed the first parathyroid exploration and adenoma resection. Mandl noted improvement of the patient's severe skeletal abnormalities postoperatively, thereby linking hyperparathyroidism with bone disease. Albright later described the clinical entity of classic primary hyperparathyroidism in the 1930s on the basis of 17 cases from his clinical practice.1 Historically, the disorder was marked by characteristic skeletal changes, nephrolithiasis, and neuromuscular dysfunction.2
Primary hyperparathyroidism is now a different entity. Since the advent of chemical screening with an autoanalyzer in the 1960s, most cases are discovered in asymptomatic patients with hypercalcemia.3,4,5,6,7,8,9,10,11,12,13 Patients may also present with nonspecific complaints of back pain, or they may have osteopenia, as depicted on radiographic studies.14,15,16,17,18,19,20 Primary hyperparathyroidism is the most common cause of hypercalcemia in the outpatient population, and it is second only to malignancy as an etiology of hypercalcemia in the inpatient population. The natural progression of disease in asymptomatic patients is unclear.21
For excellent patient education resources, visit eMedicine's Bone, Joint, and Muscle Center, Osteoporosis and Bone Health Center, and Endocrine System Center. Also, see eMedicine's patient education articles Bone Mineral Density Tests and Vitamin D: Vital Role in Your Health.
Related eMedicine topics:
Hyperparathyroidism, Secondary
Osteoporosis
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Resource Center Chronic Kidney Disease: Mineral and Bone Disorders
Resource Center Osteoporosis
Resource Center Thyroid Disease
CME ASN 2007: Emerging Therapies for Management of Mineral Bone Disorders in Chronic Kidney Disease
CME Expert Interview - The Role of Hyperphosphatemia and Phosphate Binders in Vascular Calcification: An Expert Interview With Keith A. Hruska, MD
Pathophysiology
Normal parathyroid glands function to maintain appropriate serum calcium concentrations and to regulate bone metabolism by means of the production of parathyroid hormone (PTH). In the nonpathologic state, PTH secretion increases in response to low serum calcium concentrations and enhances the synthesis of 1,25-dihydroxyvitamin D. PTH and 1,25-dihydroxyvitamin D act together to increase calcium reabsorption in the gut and kidney and to promote osteoclastic resorption and the demineralization of bone.
Primary hyperparathyroidism is caused by an overproduction of PTH, in excess of the amount required by the body. In contrast, secondary hyperparathyroidism involves an increase in PTH levels to meet some bodily requirement. In 75-80% of cases of primary hyperparathyroidism, one or more adenomas account for the overproduction, whereas approximately 20% of cases are secondary to diffuse hyperplasia of all glands. Carcinoma accounts for less than 2% of all cases.
The effects of hyperparathyroidism on bone are numerous. Excess PTH results in an increase in bone breakdown by means of osteoclastic resorption with subsequent fibrous replacement and reactive osteoblastic activity. The bone may have microfractures, with subsequent hemorrhage and growth of fibrous tissue and an influx of macrophages. The resulting mass is called a brown tumor because of the brown color of the vascular elements and blood in the mass. The process of bone resorption and fibrous replacement results in the characteristic radiologic features of generalized bone demineralization, resorption, cysts, brown tumors, erosion of the dental lamina dura, and pathologic fractures (see Images 13-16).
Other effects of hypercalcemia include nephrolithiasis or nephrocalcinosis, neurologic changes, peptic ulcer disease, and pancreatitis.
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Hypocalcemia
Pancreatitis, Chronic
Parathyroid Adenoma
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Frequency
United States
The incidence of primary hyperparathyroidism is approximately 25-30 cases per 100,000 people. In individuals aged 15-65 years, the incidence increases to 70-150 cases per 100,000 people. The disease is rare in children.
International
In Europe, the overall incidence of primary hyperparathyroidism is similar to the incidence in the United States.
Mortality/Morbidity
There is supportive evidence of an increase in the morbidity and mortality rates in patients with hyperparathyroidism that is primarily related to cardiac disease. This topic is controversial, with the results of some studies refuting the increased risk. Differences in mortality data may reflect the different clinical profiles of classic primary hyperparathyroidism and the modern asymptomatic cohort of patients. (See also Special Concerns.)
Sex
The incidence of primary hyperparathyroidism in women is 2-3 times the incidence in men.
Age
The average patient age at diagnosis is 55 years.
- The incidence peaks in those aged 40-70 years.
- The disease is rare in children.
Anatomy
Usually, 4 parathyroid glands develop, although approximately 10% of people may have 2, 3, or 5 parathyroid glands. The superior glands are typically located on the posterior aspect of the upper thyroid, whereas the location of the inferior glands is more variable. The inferior glands may be posterior to the inferior aspect of the thyroid or ectopically located in the thyroid gland, along the carotid sheath, or attached to the thymus. The superior glands may also be ectopic and in a retroesophageal, retrotracheal, or retropharyngeal location. Typical parathyroid glands are approximately 5 X 3 X 1 mm.
Related eMedicine topic:
Thyroid Anatomy
Presentation
Historically, in classic primary hyperparathyroidism, nephrolithiasis was noted in 50% of patients, and this condition was the most common clinical presentation of the disease. Currently, stone disease is present in 10-20% of patients and continues to be the most common complication that is clearly attributable to primary hyperparathyroidism. However, patients typically present without symptoms after routine laboratory testing reveals hypercalcemia. Patients may also report nonspecific back pain.
Additional manifestations of primary hyperparathyroidism include a wide range of neuromuscular and neuropsychiatric symptoms, pancreatitis, peptic ulcer disease, and cardiovascular abnormalities. Symptomatic bone disease may be present in 10-25% of patients. The diagnosis is based on an elevated PTH level in the setting of elevated calcium levels. Other chemical alterations that support the diagnosis include hypophosphatemia, hyperphosphaturia, elevated uric acid levels resulting from tissue destruction, and increased alkaline phosphatase levels resulting from bone formation.
Hereditary hyperparathyroidism is seen in multiple endocrine neoplasia type 1 syndrome (MEN 1) in association with tumors of the anterior pituitary gland and pancreas (see Images 19-22). Hyperparathyroidism develops in 95% of patients with MEN 1, and hypercalcemia occurs in those aged 10-30 years.
In multiple endocrine neoplasia type 2a syndrome (MEN-2a), parathyroid disease is infrequent and occurs in conjunction with medullary cancer of the thyroid and pheochromocytoma. Two rare hereditary syndromes include an inherited form of primary hyperparathyroidism that is not associated with other endocrine tumors and a hyperparathyroidism–jaw tumor syndrome. In patients with the latter, fibrous jaw tumors are seen with parathyroid adenomas and potentially with thyroid cancer, renal cysts, and Wilms tumors.
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Preferred Examination
Parathyroid imaging
To image the parathyroid glands before a repeat operation for recurrent or persistent disease, technetium-99m sestamibi (99m Tc MIBI) scanning or magnetic resonance imaging (MRI) are the preferred imaging modalities because of their high sensitivities in depicting ectopic or mediastinal glands.22,23,24,25,26,27
99m Tc MIBI imaging has a sensitivity of 70-95% in depicting parathyroid tumors, and this modality allows 3-dimensional (3-D) imaging with anterior-to-posterior localization of the tumor. Studies reveal equal sensitivities of99m Tc MIBI imaging and MRI in the localization of abnormal glands before a repeat surgery, with sensitivities of 82-85%. By combining the 2 modalities, the sensitivity increases to 94%.
Ultrasonography may be preferred for initial preoperative tumor localization, if desired by the surgeon, because of this technique's low risk, low cost, and high sensitivity in depicting parathyroid glands that are not ectopic or in the mediastinum.28,29 However, many surgeons believe that the initial 4-gland exploration enables a 95% cure rate with little morbidity and that initial preoperative localization provides no improvement in the outcome. Some surgeons advocate initial localization to guide directed dissection, obviating bilateral exploration. Opponents argue that the sensitivities of imaging modalities are not sufficient and that parathyroid glands can be missed in an unacceptable number of patients.
Musculoskeletal imaging
The diagnosis of primary hyperparathyroidism is made by means of the laboratory confirmation of an elevated PTH level in the setting of hypercalcemia.
Radiologically, radiographs may yield the most specific findings that are consistent with the disorder, and radiography is the preferred examination when the clinical findings suggest primary hyperparathyroidism. Radiographs of the hands may yield the diagnostic finding of subperiosteal resorption, which is virtually pathognomonic for the disease (See Images 2-4 and 23). If radiographs of the hands reveal no abnormalities, other sites are unlikely to demonstrate abnormal findings. Dual-energy x-ray absorptiometry (DXA) and quantitative CT (QCT) scanning may provide evidence of osteoporosis that is consistent with the diagnosis; however, the finding is nonspecific for primary hyperparathyroidism.
Limitations of Techniques
Radiographs of the hand may yield the pathognomonic finding of subperiosteal resorption, which is consistent with a diagnosis of primary hyperparathyroidism. However, other findings on radiographs are not specific for this disorder. In addition, DXA and QCT scanning are the preferred diagnostic modalities for the evaluation of osteoporosis, which is one of the most common findings in patients with primary hyperparathyroidism. However, osteoporosis may be associated with a host of other diagnoses; therefore, the specificity of this condition may be limited. Currently, the diagnosis of primary hyperparathyroidism is primarily based on the laboratory confirmation of elevated PTH concentrations in the setting of an increased calcium level.
Differential Diagnoses
Other Problems to Be Considered
Osteoarthritis, Secondary
Reiter Syndrome, Musculoskeletal
The differential diagnosis depends on which of the many possible findings of primary hyperparathyroidism are being considered and the imaging modality used.
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References
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Further Reading
Keywords
von Recklinghausen's disease of bone, von Recklinghausen disease of bone, generalized osteitis fibrosa cystica, PTH, parathyroid glands, multiple endocrine neoplasia syndrome type 1, MEN 1 / MEN-1, brown tumor
