Study Finds Hyperparathyroidism in 25% of XLH Patients

Study Finds Hyperparathyroidism in 25% of XLH Patients
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Hyperparathyroidism, a condition in which the parathyroid gland produces an excess of parathyroid hormone, is found in 25% of people with X-linked hypophosphatemia (XLH), a study has found.

The study, “Hyperparathyroidism in patients with X‐linked hypophosphatemia,” was published in the Journal of Bone and Mineral Research.

The parathyroid gland is responsible for producing parathyroid hormone (PTH), which ensures normal levels of calcium in the blood. If calcium levels get too low, the body responds by secreting the hormone, which can recruit calcium from bone material and other sources.

Hyperparathyroidism can lead to chronically high blood calcium levels, or hypercalcemia. Among its different subtypes, primary hyperparathyroidism is most commonly caused by a benign tumor, while secondary hyperparathyroidism refers to damage in another organ system that leads to excess PTH production by the parathyroid gland.

Secondary hyperparathyroidism has been observed in XLH, which is characterized by low levels of phosphate in the blood. Prolonged use of phosphate supplements, a standard treatment in XLH, was thought to cause such high PTH levels. However, more recent evidence has found hyperthyroidism in XLH patients not treated with phosphate supplements.

To better understand the connection between XLH and secondary hyperthyroidism, a team at the Hôpital Bicêtre, in France, collected data from a total of 68 patients from 2011 to 2017. This was compared with data from 136 healthy controls who had provided blood samples in the VARIETE clinical trial (NCT01831648).

Two controls were matched to each patient by age, sex, and blood levels of a vitamin D3 biomarker called calcifediol.

As expected, the blood level of phosphate was significantly lower in XLH patients. While the calcium level was not different between the two groups, those with XLH had higher levels of PTH.

Seventeen patients (25%) had blood levels of PTH in the hyperparathyroidism range, compared with 3 (2%) of the controls. The findings indicated that the difference was not driven by gender. One of the 17 XLH patients had never taken phosphate supplements, while six had not taken supplements for 19 years, on average.

“These observations argue against a major role of intermittent hyperphosphatemia in the occurrence of hyperparathyroidism,” the researchers wrote.

Among patients with hyperparathyroidism, seven showed hypercalcemia, defined as calcium concentrations above 2.55 mmol/L. The median age of these patients at diagnosis was 33.

All seven underwent surgery to remove the parathyroid gland. Signs of tumorous growths and enlargement of parathyroid cells were discovered. Following the procedure, the patients showed normal blood calcium and a nearly 65% reduction in PTH levels over an average of 44 months, indicating that the surgery was successful.

“Hypercalcemic hyperparathyroidism affects young patients and can be effectively and safely cured by selective surgical resection of the pathological parathyroid glands,” the team wrote.

Higher PTH levels were associated with greater calcium levels and lower phosphate levels in XLH patients, “suggesting an altered regulation of parathyroid function,” the scientists added.

“In conclusion, this is the first evaluation of parathyroid function in XLH adult patients,” they wrote. “Hyperparathyroidism is frequent, affecting 25% of patients.”

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