eMedicine Specialties > Radiology > Musculoskeletal

Hyperparathyroidism, Secondary

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
Coauthor(s): Farrah Jabeen, MB, BCh, MRCS, FRCR, House Officer, Radiology Training Program, North West Deanery, UK; Sumaira MacDonald, MBChB, PhD, MRCP, FRCR, Lecturer, Sheffield University Medical School; Endovascular Fellow, Sheffield Vascular Institute
Contributor Information and Disclosures

Updated: Nov 5, 2008

Introduction

Background

Secondary 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.

Related eMedicine Radiology topic:
Hyperparathyroidism, Primary

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Pathophysiology

Secondary 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.¹ Chronic hypocalcemia and secondary hyperparathyroidism can also be products of pseudohypoparathyroidism, vitamin D deficiency,^2,3 and intestinal malabsorption syndromes that are characterized by inadequate vitamin D and calcium absorption.

Long-term furosemide therapy in infants, the use of oral contraceptives, and idiopathic hypercalciuria are other, highly unusual causes of secondary hyperparathyroidism.

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 preexisting 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.

There is considerable speculation as to why secondary hyperparathyroidism is frequently accompanied by osteosclerosis. Two possibilities are as follows: 

• Excessive PTH directly acts as an anabolic agent on the bone, causing osteosclerosis.
• A significant increase in the formation of woven bone contributes to the osteosclerotic appearance.

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,^2,3 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.

Frequency

United States

Renal osteodystrophy is present in almost all patients with chronic advanced renal failure.

Mortality/Morbidity

Renal 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.

Race

No racial predilection exists.

Sex

Males and females are affected equally.

Age

Secondary hyperparathyroidism is more common in children than in adults.

Presentation

Features 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 Examination

Radiographs 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.⁴

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 Techniques

Subperiosteal 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.

Differential Diagnoses

Other Problems to Be Considered

Familial hyperparathyroidism
Tertiary hyperparathyroidism
Conditions involving ectopic parathyroid production (eg, bronchogenic carcinoma, renal cell carcinoma)
Thymoma as a cause of a true ectopic hyperparathyroidism
Multiple endocrine neoplasia type IIA
Other metabolic bone diseases
Osteoarthritis, secondary
Reiter syndrome, musculoskeletal

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