Normocalcemic primary hyperparathyroidism: How new technology affects an old diagnosis

June 11, 2007
Surgical Rounds®, June 2007, Volume 0, Issue 0

Christian G?lvez-Padilla, Resident, Department of Surgery; Joanne Favuzza, Resident, Department of Surgery; Eugene Curletti, Associate Professor of Surgery, Department of Surgery, University of Massachusetts Medical School, Berkshire Medical Center, Pittsfield, MA

Christian G?lvez-Padilla, MD

Resident

Department of Surgery

Joanne Favuzza, DO

Resident

Department of Surgery

Eugene Curletti, MD

Associate Professor of Surgery

Department of Surgery

University of Massachusetts

Medical School

Berkshire Medical Center

Pittsfield, MA

Primary hyperparathyroidism is characterized by hypercalcemia, hypophosphatemia, and elevated serum parathyroid hormone (PTH) levels. Normally, PTH acts on the bones to stimulate calcium release and on the kidneys to reabsorb tubular calcium. When there are chronic elevations of PTH, the hormone's normal functions on the bones and kidneys are exacerbated significantly, resulting in hypercalcemia.1

Occasionally, hyperparathyroidism may occur in the setting of normal calcium levels. Normocalcemic hyperparathyroidism, especially in postmenopausal women, is often detected due to increased screening for osteoporosis using bone density testing. We report the case of a patient with osteoporosis who presented with normocalcemic hyperparathyroidism. This patient had no secondary causes of elevated PTH and underwent 3½-gland parathyroidectomy.

Case report

An 84-year-old white woman presented to our institution with a 3-year history of worsening bone density loss. She had been evaluated for this problem in the past, after she had presented with nontraumatic thoracic vertebrae compression fractures (Figure). Bone densitometry was performed showing decreased bone mass and a 10% to 15% loss compared with an evaluation 3 years earlier. The patient was started on pamidronate, and her serum calcium and phosphate levels were between normal ranges. Ultrasonography of the neck and a Sestamibi scan were undertaken, which showed no abnormalities or uptake.

One year after starting treatment with pamidronate, the patient was continuing to lose bone density. After a surgical consultation, she underwent exploration of the neck. Four normal-sized parathyroid glands were found. After frozen-section confirmed parathyroid tissue, a 3½-gland parathyroidectomy was performed. Thirty minutes after the resection, the patient's preoperative intact PTH level of 164 pg/mL dropped to 32 pg/mL. She had an uneventful recovery and was discharged from the hospital on postoperative day 1.

Discussion

The diagnosis of primary hyperparathyroidism generally is made when hypercalcemia is found during routine biochemical studies. Our case involves a patient with primary hyperparathyroidism and normal calcium levels, which is known as normocalcemic primary hyperparathyroidism. This condition was first described by Mather in 1953, when he reported a case of osteitis fibrosa cystica in a 33-year-old patient whose symptoms were relieved after surgical removal of a parathyroid adenoma.2

Some studies have attributed normocal-cemic hyperparathyroidism to clinicians using the indirect measurement of serum total calcium concentration instead of the more direct measurement of serum ionized calcium concentration.3 Another explanation is that the disease has two phases.4 In the first phase, calcium levels are usually normal, and most patients' condition is not detected until the second phase, when hypercalcemic hyperparathyroidism develops.

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As this case report demonstrates, nor-mocalcemic hyperparathyroidism is especially common in postmenopausal women undergoing bone density screenings for osteoporosis.5 Using the biphasic theory of disease progression, studies have shown that the detrimental effects on the bones occur during the normocalcemic phase of the disease.6 Melton and associates' retrospective study showed an increased incidence of fractures during the first phase of the disease compared with the second phase.7 A study by Maruani and colleagues compared ionized calcium concentrations and renal function in normocalcemic and hypercalcemic hyperparathyroid patients. This study found that approximately 20% of primary hyperparathyroid patients were normocalcemic. Although the groups were similar in age, sex, and serum PTH levels, the serum ionized calcium in the normocalcemic group was found to be 1.32 mmol/L versus 1.45 mmol/L for the hypercalcemic group 0.05). The normocalcemic group also had significantly lower fasting urinary calcium excretion and a lower index of tubular calcium reabsorption. These are measures of net bone calcium release and the kidney's ability to reabsorb calcium, respectively8 Based on these data, patients with normocalcemic hyperparathyroidism were thought to maintain normal calcium levels due to the bones and kidneys resisting the effects of PTH.

The treatment of choice in patients with primary hyperparathyroidism is parathyroidectomy. Patients with normocalcemic hyperparathyroidism also benefit from removal of the parathyroid glands. In a study by Siperstein and associates, normocalcemic hyperparathyroid patients had similar improvements in preoperative symptoms after surgical intervention as their hypercalcemic counterparts.9 In addition, other studies have shown skeletal remineralization after surgery for primary hyperparathyroidism.10

Conclusion

Clinicians increasingly may encounter patients with normocalcemic hyperparathyroidism due to technological advances such as bone density testing, which is being performed more routinely, especially in postmenopausal women. Identifying these patients is important because of the consequences of untreated hyperparathyroidism, which include osteoporosis and vertebral compression fractures. Once the condition is identified parathyroidectomy should be undertaken.

References

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