You are in: eMedicine Specialties > Radiology > MUSCULOSKELETAL Hyperparathyroidism, SecondaryArticle Last Updated: Dec 18, 2007AUTHOR AND EDITOR INFORMATIONSection 1 of 10
  Author: Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR, LRCP, Chairman of Medical Imaging, Professor of Radiology, NGHA, King Fahad National Guard Hospital, King Abdulaziz Medical City, Riyadh, Saudi Arabia Ali Nawaz Khan is a member of the following medical societies: American Institute of Ultrasound in Medicine, Radiological Society of North America, Royal College of Physicians, Royal College of Physicians and Surgeons of the United States, Royal College of Radiologists, and Royal College of Surgeons of England Coauthor(s): Farah Jabeen, MBChB, MRCS; Sumaira MacDonald, MBChB, PhD, MRCP, FRCR, Lecturer, Sheffield University Medical School; Endovascular Fellow, Sheffield Vascular Institute Editors: Leon Lenchik, MD, Director, Densitometry Minifellowship, Assistant Professor, Department of Radiology, Wake Forest University Medical Center; Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand; Wilfred CG Peh, MD, MBBS, FRCP(Glasg), FRCP(Edin), FRCR, MHSM, Clinical Professor, Faculty of Medicine, National University of Singapore; Senior Consultant Radiologist, Programme Office, Singapore Health Services; Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute; Felix S Chew, MD, MBA, EdM, Professor, Department of Radiology, Vice Chairman for Radiology Informatics, Section Head of Musculoskeletal Radiology, University of Washington Author and Editor Disclosure Synonyms and related keywords: osteitis fibrosa cystica, renal osteodystrophy, pronounced parathyroid gland hyperplasia, end-organ resistance to parathyroid hormone, PTH, chronic renal insufficiency, parathyroid glands INTRODUCTIONSection 2 of 10
  BackgroundSecondary hyperparathyroidism is characterized by pronounced parathyroid gland hyperplasia resulting from end-organ resistance to parathyroid hormone (PTH). The consequent hypersecretion of PTH depresses calcium levels. The most important cause of secondary hyperparathyroidism is chronic renal insufficiency. The clinical manifestation of secondary hyperparathyroidism includes bone and joint pain, as well as limb deformities. The characteristics of the disease that are displayed radiologically in the skeleton are similar to those of primary hyperparathyroidism. (See also the eMedicine articles Hyperparathyroidism [in the Pediatrics section], Hyperparathyroidism [in the Emergency Medicine section], Hyperparathyroidism [in the Otolaryngology and Facial Plastic Surgery section], Hyperparathyroidism [in the Endocrinology section], and Hyperparathyroidism, Primary.) PathophysiologySecondary hyperparathyroidism is often accompanied by pronounced hyperplasia of the parathyroid gland's chief cells. All 4 glands are usually affected by this hyperplasia, but in some cases, for reasons that remain obscure, only 1 or 2 are involved. A true adenoma may develop, but only in rare instances. Histologically, islands of oxyphils are often present, and hyperplastic cells usually replace the fat. Secondary hyperparathyroidism most commonly results from chronic renal disease, which can develop in hemodialysis patients. Chronic hypocalcemia and secondary hyperparathyroidism can also be products of pseudohypoparathyroidism, vitamin D deficiency, and intestinal malabsorption syndromes that are characterized by inadequate vitamin D and calcium absorption. In most cases, the sequence of events leading to the development of PTH hypersecretion is any long-standing osteomalacia. The most common cause is chronic renal insufficiency, such as that in renal polycystic disease or chronic pyelonephritis. Chronic renal insufficiency is accompanied by several biochemical abnormalities, including diminished urinary excretion of phosphate with consequent elevation of serum phosphate levels and elevation in the levels of the calcium-phosphate product. Serum calcium levels tend to be normal, but they may be marginally reduced. The alkaline phosphates are almost always elevated. The hyperphosphatemia and damaged renal parenchyma lead to a reduction of renal production of 1,25-dihydroxycholecalciferol (1,25-DHCC). Decreased intestinal absorption of vitamin D3 follows, impairing the mobilization of calcium from the bones as a result of PTH resistance. Aluminum accumulates in patients undergoing long-term hemodialysis. This accumulation causes dementia and, owing to a poorly understood mechanism, also prevents the mineralization of osteoid. The bone changes that may occur with aluminum toxicity include osteopenia, fractures, and osteomalacia. An early sign of aluminum toxicity is periosteal new-bone formation along the shafts of long bones and at the pelvic inlet. Low or normal serum calcium levels usually indicate pre-existing osteomalacia. A markedly elevated alkaline phosphatase level typically accompanies skeletal disease. The most common presentation of renal osteodystrophy is a combination of osteomalacia, secondary hyperparathyroidism, and a varying degree of osteosclerosis. Several pathologic changes occur in association with renal osteodystrophy. These include lacunar bone resorption, fibrous replacement of the marrow following hemorrhage, necrosis, and brown tumors caused by intense osteoclastic activity in some areas. The skeletal changes in children are typically the same as those occurring in rickets; they affect the epiphyseal plate, as demonstrated through the use of undecalcified preparations. (See also the eMedicine article Osteomalacia and Renal Osteodystrophy.) There is considerable speculation as to why secondary hyperparathyroidism is frequently accompanied by osteosclerosis. Two possibilities are as follows:
Hyperuricemia is often found with chronic renal insufficiency, which in rare instances manifests as gout. Another complication of chronic renal disease is oxalosis, in which oxalate deposition occurs in growth plates, metaphyses, and intervertebral plates. With appropriate treatment, such as renal transplantation or vitamin D supplementation, the changes related to secondary hyperparathyroidism may resolve. Long-standing secondary hyperparathyroidism associated with extensive glandular hyperplasia may not revert. In the patients with this condition, the presence of tertiary hyperparathyroidism should be considered. The tertiary condition develops in patients with long-standing secondary hyperparathyroidism, which stimulates the growth of an autonomous adenoma. A clue to the diagnosis of tertiary hyperparathyroidism is the presence of intractable hypercalcemia and/or an inability to control osteomalacia despite vitamin D therapy. FrequencyUnited StatesRenal osteodystrophy is present in almost all patients with chronic advanced renal failure. Mortality/MorbidityRenal osteodystrophy progresses despite intermittent hemodialysis. Bone pain from renal osteodystrophy can slowly progress until the patient is bedridden. In some patients, secondary hyperparathyroidism responds to the control of phosphate and calcium levels, as well as to vitamin D therapy. Such measures may lead to improved homeostasis of calcium and phosphorus levels and may reverse the symptoms of bone pain and PTH suppression. In some patients, the disease responds to renal transplantation. However, not all cases respond to these measures, and parathyroidectomy may be required. RaceNo racial predilection exists. SexMales and females are affected equally. AgeSecondary hyperparathyroidism is more common in children than in adults. Clinical DetailsFeatures of renal failure or other conditions are associated with secondary hyperparathyroidism. Symptoms associated with renal osteodystrophy usually appear with advanced renal failure, although biochemical abnormalities appear early and should prompt treatment to prevent irreversible bone changes. Bone and joint pains may develop and slowly progress until the patient is bedridden. The pain is usually vague and is commonly located in the lower back, hips, knees, and legs. Severe lower back pain occurs as a result of a collapsed vertebral body, and a spontaneous rib fracture can cause sharp chest pain. Joint pain may also occur as a result of the periarticular deposition of hydroxyapatite crystals; this pain particularly occurs in marked hyperphosphatemia. Rarely, avascular necrosis of the femoral head may occur in association with renal osteodystrophy, causing pain and limping. Muscular weakness is usually proximal; it progresses slowly and usually responds to vitamin D therapy. Pruritus may occur as a result of calcium deposition in renal insufficiency, particularly in patients with severe hyperparathyroidism. In children with azotemia, skeletal deformities are common. These deformities include bowing of the tibia and femur, as well as deformity resulting from a slipped femoral epiphysis. In adult patients with chronic renal failure, particularly those with predominant osteomalacia, lumbar kyphoscoliosis and deformity of the thoracic cage may be present. Growth reduction is generally observed in young children before and during hemodialysis. Vascular calcification and peripheral ischemic necrosis may cause violaceous discoloration of the skin of the fingers and toes. Sometimes, associated ulceration and scar formation are present. An association with mitral and aortic stenosis has been described. Preferred ExaminationRadiographs are the mainstays of the radiologic diagnosis of secondary hyperparathyroidism, because the predominant changes are skeletal, with abnormal calcifications at various sites; these calcifications are well depicted on conventional radiographs.1 The changes observed on radionuclide studies are not consistent or specific. The diagnosis is made or incidentally suggested because radionuclide investigation is initially performed for the evaluation of conditions other than secondary hyperparathyroidism, such as bone pain. Similarly, computed tomography (CT) scan findings are usually incidental, and CT scanning is not specifically performed for the diagnosis of secondary hyperparathyroidism. Ultrasonography may be useful in evaluating enlarged parathyroid glands. Limitations of TechniquesSubperiosteal erosions, periosteal reactions, and several other osseous abnormalities in secondary hyperparathyroidism are not specific for the disease and may occur in other skeletal disorders or conditions, as well as in primary hyperparathyroidism. The exact sensitivity of plain radiography in the diagnosis of secondary hyperparathyroidism is not known, but the fact that biochemical abnormalities may precede radiologic change is well recognized. Radionuclide findings are not specific, and pure osteomalacia and primary hyperparathyroidism can result in an appearance similar to that of secondary hyperparathyroidism. As with radiographic findings, CT scan depictions of the osseous changes are nonspecific. Ultrasonography may not always show hyperplasia of the parathyroid glands. DIFFERENTIALSSection 3 of 10
Adamantinoma Ankylosing Spondylitis Bone Metastases Calcium Pyrophosphate Deposition Disease Chondroblastoma Crohn Disease Eosinophilic Granuloma, Skeletal Ewing Sarcoma Fibrous Dysplasia Gout Hyperparathyroidism, Primary Osteoblastoma Osteomalacia and Renal Osteodystrophy Osteomyelitis, Acute Pyogenic Osteomyelitis, Chronic Osteoporosis, Involutional Psoriatic Arthritis Rheumatoid Arthritis, Hands Rheumatoid Arthritis, Spine Rickets Ulcerative Colitis Other Problems to Be ConsideredFamilial hyperparathyroidism RADIOGRAPHSection 4 of 10
FindingsRadiography is the most important investigational modality in the diagnosis of secondary hyperparathyroidism; radiographs may show several skeletal abnormalities. The radiologic features of secondary hyperparathyroidism are similar to those of the primary form of the disease. The combination of 2 pathologic processes of hyperparathyroidism and osteomalacia and/or rickets is responsible for the osseous abnormalities in renal osteodystrophy.2 In children, widening of the growth plates of the long bones may be present, with irregularity of the metaphyseal margins and disorganization of the growth plate, which is indicative of advanced rickets. These changes of gross disease have been likened to the rotting of a wooden post at its stem. Severe osteopenia may be complicated by pathologic fractures. Epiphyseal displacement of metaphyseal fractures may be present; the most commonly involved sites include the distal radius, the proximal humerus, the distal femur, and the heads of metacarpal and metatarsal bones. Skeletal maturation may be retarded. Lateral Blount disease may occur as a result of lateral angulation of the proximal tibial epiphysis and genu valgum. Jaw enlargement has been described. In adults, subperiosteal bone resorption characteristically affects the phalangeal tufts, the radial aspect of the proximal and middle phalanges of the fingers, the metatarsals, the rib margins, the lamina dura, and the medial margins of the proximal humerus, femur, and tibia. Brown tumors occur, but these are less common with secondary hyperparathyroidism than they are with primary hyperparathyroidism. However, as the life expectancy of patients with chronic renal disease has increased, brown tumors have increasingly been identified with renal osteodystrophy. Brown tumors may occur in the spine and form expansile masses, which can be complicated by paraplegia. Brown tumors of the sellar and/or parasellar regions and face may appear as destructive lesions. The skull may show a granular pattern, which may be associated with thickening, particularly in the inner table. Osteomalacia may be predominant in patients with renal osteodystrophy. Associated Looser transformation zones and pathologic fractures, possibly symmetric, can be present. Osteosclerosis may affect the epiphyses, metaphyses, pelvis, and ribs. Frequently, a classic rugger-jersey spine is observed; it is caused by ill-defined bands of increased bone density adjacent to the vertebral endplates. An organized periosteal reaction (eg, periosteal neostasis) may develop around the metatarsals, femora, and pelvis. This finding, although not typical, is more common in secondary hyperparathyroidism than it is in the primary form of disease. Generalized osteopenia, often severe, may occur. Digital phalangeal brachydactyly secondary to healed renal osteodystrophy may be present. Rarely, kyphoscoliosis may occur. Extra-osseous calcification is more common in secondary hyperparathyroidism than it is in the primary form of the disease, and it is even more common in long-standing disease. Abnormal calcification and other abnormalities include the following:
See also the eMedicine articles Cardiac Calcifications, Breast, Benign Calcifications, and Chondrocalcinosis. Degree of ConfidenceIn renal osteodystrophy, bone resorption is invariably present. Correlation of findings with the patient's history and biochemical parameters should lead to the correct diagnosis. However, secondary hyperparathyroidism associated with osteomalacia of dietary origin may cause vague symptoms and, sometimes, nonspecific biochemical findings. False Positives/NegativesThe radiologic features of secondary hyperparathyroidism are similar to those of the disease's primary form. The radiologic changes can sometimes mimic those observed in Paget disease. CT SCANSection 5 of 10
FindingsCT scan findings in renal osteodystrophy include abnormal sacroiliac joints, multiple brown tumors, osteitis fibrosa cystica, prominent Schmorl nodes, periarticular tumoral calcifications, and slipped capital femoral epiphyses.3 Layering of soft-tissue calcification is well demonstrated on CT scans. In general, however, and in comparison with other modalities, CT scanning offers no advantage in the diagnosis of secondary hyperparathyroidism. Degree of ConfidenceCT scanning is rarely employed in screening exams for renal osteodystrophy.3 Nonetheless, knowledge of the CT scan appearances of secondary hyperparathyroidism is important; it helps clinicians avoid confusing the changes associated with secondary hyperparathyroidism with those resulting from other pathologic conditions. On the whole, however, CT scanning is not sensitive in the detection of changes related to secondary hyperparathyroidism. False Positives/NegativesSoft-tissue calcification is not specific to secondary hyperparathyroidism and has myriad causes. Erosive changes attributable to secondary hyperparathyroidism may easily be confused with changes in rheumatoid arthritis, seronegative spondyloarthropathies, infection, or even malignancy. Brown tumors and amyloid deposition can easily be mistaken for a neoplastic process. MRISection 6 of 10
FindingsMRI can adequately reveal skeletal deformity, cortical thickening, and irregular trabecular patterns in children with renal osteodystrophy.3, 4 In addition, MRI shows osteonecrosis and intraosseous soft-tissue masses more conspicuously than do plain radiographs. This modality also shows diffuse, nonspecific marrow changes.5 One case describes the MRI diagnosis of thoracic myelopathy caused by spinal stenosis secondary to renal osteodystrophy.6 MRI is also useful in the detection of parathyroid hyperplasia. Degree of ConfidenceBased on current experience, MRI findings in secondary hyperparathyroidism are not specific enough for this modality to replace radiography. Also, MRI has low sensitivity and specificity in the detection of parathyroid hyperplasia. False Positives/NegativesMRI findings in chronic osteodystrophy can often mimic those of other diseases. ULTRASOUNDSection 7 of 10
FindingsUltrasonography is useful in the detection of parathyroid enlargement. Degree of ConfidenceThe sensitivity of ultrasonography in the detection of parathyroid hyperplasia is low. Imaging modalities in secondary hyperparathyroidism are of a limited value in guiding medical and surgical treatment. However, if percutaneous alcohol ablation is contemplated as an adjunct to medical treatment, ultrasonography may be useful in the initial localization of an abnormal gland. False Positives/NegativesUltrasonography has a high rate of false-negative findings in the diagnosis of parathyroid hyperplasia. A thyroid tumor may mimic a parathyroid adenoma. NUCLEAR MEDICINESection 8 of 10
FindingsSeveral radionuclide features are reported in secondary hyperparathyroidism. A superscan may reveal the following findings:
Technetium-99m sestamibi and subtraction scintigraphy with thallium-201 (201Tl) and 99mTc have been used to localize parathyroid hyperplasia in secondary hyperparathyroidism, but they are of limited value.7, 8, 9, 10 Degree of ConfidenceRadionuclide bone scans have low sensitivity and specificity in the detection of secondary hyperparathyroidism. The use of radionuclides in the diagnosis of parathyroid hyperplasia also has a limited role. False Positives/NegativesBesides renal osteodystrophy and/or hyperparathyroidism, the following conditions, displaying the same features as hyperparathyroidism, may appear to be present:
MULTIMEDIASection 9 of 10
REFERENCESSection 10 of 10
Hyperparathyroidism, Secondary excerpt Article Last Updated: Dec 18, 2007 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
