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Pediatric Hyperparathyroidism Workup

  • Author: Gordon L Klein, MD, MPH; Chief Editor: Stephen Kemp, MD, PhD  more...
 
Updated: Dec 03, 2014
 

Laboratory Studies

One key difference between primary and secondary hyperparathyroidism is that patients with primary disease are always hypercalcemic, whereas those with secondary disease are almost always normocalcemic. For blood studies, serum calcium concentrations and immunoreactive parathyroid hormone (PTH) levels using immunoradiometric assay (IRMA) to detect intact PTH molecules are most important. These can be used to distinguish primary hyperparathyroidism from secondary hyperparathyroidism. In primary disease, high levels of calcium and PTH are observed, whereas in secondary disease, levels of calcium are within the reference range and levels of PTH are high.

Serum levels of phosphorus are not always helpful with respect to diagnosis. Note the following:

  • Serum phosphorus levels in primary hyperparathyroidism are mainly in the low-normal range.
  • Serum levels in secondary hyperparathyroidism due to renal failure serum phosphorus levels are elevated because of the inability of the kidney to excrete phosphorus.
  • Hypercalciuria (urinary calcium levels >250 mg/d in women and 300 mg/d in men) can be seen in as many as 30% of adult cases. [2]
  • In the absence of dialysis therapy, phosphorus levels are elevated.
  • In some cases of chronic cholestatic liver disease, serum phosphorus levels are low.

Tests for the following biochemical markers of bone formation are elevated because of the high turnover state. This high turnover state is not specific to hyperparathyroidism of either primary or secondary origin and could be equally compatible with Paget disease or other high turnover states. Note the following:

  • Serum levels of osteocalcin or bone-specific alkaline phosphatase
  • Biochemical markers of bone resorption, such as serum C-telopeptide of type I collagen
  • Urinary N-telopeptide (NTx), C-telopeptide of type I collagen (CTX)
  • Deoxypyridinoline

Note that a case has been reported describing a 14-year-old girl with a parathyroid adenoma who presented with hypercalcemia, pancreatitis, and nephrolithiasis, yet had a low serum intact PTH level.[13] A turboassay, however, showed very high PTH levels, as did a C-terminal assay. There was no mutation in the PTH gene sequence, which may well indicate that there was a post-translational modification of PTH not recognized by DNA sequencing. More than one assay may be required if there is biochemical evidence of hyperparathyroidism.

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Imaging Studies

Sestamibi scanning may be considered and is often paired with single-photon emission computerized tomography (SPECT)/CT scanning to localize the parathyroid lesions prior to surgery. Ultrasonography of the thyroid area may also be considered.

The value of skeletal radiographs in diagnosis of primary hyperparathyroidism is questionable because relatively few cases exhibit stigmata of hyperparathyroidism. Radiography may be useful in defining the extent of damage in secondary hyperparathyroidism. Cortical bone is primarily affected, as opposed to cancellous or trabecular bone.[2]

Radiography reveals the following in some cases of primary and most cases of secondary hyperparathyroidism:

  • Multiple areas of subperiosteal bone resorption of the distal phalanges
  • Tapering of the clavicles
  • Brown tumors of the long bones and a salt-and-pepper appearance of the skull: These occur in less than 5% of US patients with primary disease. [2]

Another way to monitor the severity of bony involvement is with bone densitometry, determined by dual energy x-ray absorptiometry (DEXA). This technique can be used to quantify bone mineral content of a specific region in g, bone area in cm2, and density in g/cm2. This is an areal or 2-dimensional measurement but can be followed longitudinally to evaluate the severity of the effect on bone and the effectiveness of therapy.

Bone density in the hip and lumbar spine, for which pediatric reference range values are often integrated into the computer software of the machine, are expected to be low compared with age-related reference range values. However, in adults, bone mass density is typically low in the distal third of the forearm and is relatively well maintained at the lumbar spine.[2]

The degree of improvement with treatment is hard to predict because of a lack of evidence. Patients with severe primary hyperparathyroidism have reduced bone mineral density at multiple sites, although overt bone disease is now seen in less than 5% of these patients in the United States.

The drawback to this method in children is that the pediatric bone is still growing and adapting to stresses, and changes in bone volume that will affect bone strength cannot be detected. In addition, bone density readings are size dependent. Thus, a smaller person has a falsely lower bone density than a larger person.

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Other Tests

The only other tests of value are those that are used to diagnose the underlying cause of secondary hyperparathyroidism, associated genetic defects, or tumors accompanying primary hyperparathyroidism.

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Procedures

No diagnostic procedures are pertinent to diagnosis, except those that are used to diagnose an underlying disease in secondary hyperparathyroidism.

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Histologic Findings

In most cases of primary hyperparathyroidism, an adenoma involving only 1 of 4 glands is present. Less frequently, adenomas involve multiple glands, and parathyroid carcinoma is very rare. All histologic findings have been described in adults.

In secondary hyperparathyroidism, the vast majority of cases demonstrate only chief cell hyperplasia.

In severe cases, especially with chronic renal failure, adenomas may develop and hyperparathyroidism may continue even in the absence of hyperphosphatemic stimulus. This is known as tertiary hyperparathyroidism.

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Contributor Information and Disclosures
Author

Gordon L Klein, MD, MPH Clinical Professor of Orthopedic Surgery and Rehabilitation, University of Texas Medical Branch School of Medicine

Gordon L Klein, MD, MPH is a member of the following medical societies: American Academy of Pediatrics, American Society for Nutrition, American Gastroenterological Association, American Pediatric Society, American Society for Bone and Mineral Research, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, Society for Pediatric Research

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London) Professor and Chair, First Department of Pediatrics, Athens University Medical School, Aghia Sophia Children's Hospital, Greece; UNESCO Chair on Adolescent Health Care, University of Athens, Greece

George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London) is a member of the following medical societies: American Academy of Pediatrics, American College of Physicians, American Pediatric Society, American Society for Clinical Investigation, Association of American Physicians, Endocrine Society, Pediatric Endocrine Society, Society for Pediatric Research, American College of Endocrinology

Disclosure: Nothing to disclose.

Chief Editor

Stephen Kemp, MD, PhD Former Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas for Medical Sciences College of Medicine, Arkansas Children's Hospital

Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

Phyllis W Speiser, MD Chief, Division of Pediatric Endocrinology, Steven and Alexandra Cohen Children's Medical Center of New York; Professor of Pediatrics, Hofstra-North Shore LIJ School of Medicine at Hofstra University

Phyllis W Speiser, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, Endocrine Society, Pediatric Endocrine Society, Society for Pediatric Research

Disclosure: Nothing to disclose.

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Normal parathyroid glands as seen during a thyroidectomy. The large arrow points to the superior parathyroid. The thinner arrow points to the inferior parathyroid. The forceps points toward the recurrent laryngeal nerve. The patient's head is toward the right.
 
 
 
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