Continuous PTH Infusion May Benefit Non-Responding Patients, Case Report Finds

People with hypoparathyroidism whose disease cannot be sustainably controlled with conventional treatment and parathyroid hormone (PTH) infusions may benefit from a continuous PTH infusion using an insulin pump, a case series suggests.

The approach was found to be safe and to control the disease for 5.5 years or more in three people with hypoparathyroidism. The therapy also allowed the patients to reduce their doses of other medications, the researchers said.

The study, “Continuous rhPTH (1–34) treatment in chronic hypoparathyroidism,” was published in Endocrinology, Diabetes and Metabolism Case Reports.

Hypoparathyroidism is caused by low levels of PTH in the blood. That leads to a marked decrease of calcium in the blood (hypocalcemia) and in the urine (hypocalciuria), and an increase in the amount of phosphate in circulation, called hyperphosphatemia.

The symptoms most commonly include numbness, muscle cramps, and involuntary muscle contractions. However, some patients experience neurological symptoms and kidney insufficiency in the long run.

The standard treatment for hypoparathyroidism consists of calcium and vitamin D supplementation to restore calcium back to normal levels. But some patients have severe forms of the disease that do not respond to this supplementation. They require several daily under-the-skin infusions of the missing PTH hormone, which also helps control phosphate levels.

In rare cases, however, these PTH infusions are still not enough, and patients continue to experience fluctuations in calcium levels and severe hypocalcemia, requiring additional treatment.

Researchers in Germany reported the cases of three patients whose disease could only be effectively managed with a continuous administration of PTH via an insulin pump. This allowed for long-term control of calcium levels and disease symptoms.

Among the patients were two women, ages 52 and 48, and a 58-year-old man who had had hypoparathyroidism for at least 12 years after undergoing surgery to remove the thyroid gland.

All three had experienced multiple hypocalcemic crises, despite treatment with supplements and several dose adjustments. Additional treatment with multiple PTH daily infusions provided only short-lasting benefits, with the patients still experiencing fluctuations in their calcium, vitamin D, and phosphate levels.

To help control the disease, the three individuals were started on continuous infusions of PTH, given via an insulin pump — the Omnipod pump by Insulet, the Medtronic pump by Medtronic, or the Animas Vibe pump, formerly sold by Johnson & Johnson Medical, but now discontinued. These pumps are normally used to control diabetes but can be loaded with other medicines; they enable the delivery of steady treatment doses over time.

“Within 1 week after start of pump therapy, normalization of serum [blood] calcium and phosphate levels could be observed in all three patients,” the researchers wrote. “Clinical symptoms gradually improved.”

After starting the continuous PTH infusion, the older woman had a lower frequency of seizures, which were still common with supplements and PTH infusions. The other two patients no longer had hypo- or hypercalcemic crises — which occur when supplementation brings calcium to higher-than-normal levels.

In addition, the calcium supplementation could be reduced to lower doses in all three individuals.

The treatment was able to control the disease for the first time in all of the patients, and did so for a span of 5.5 to seven years up to the study’s completion. In the long term, all three patients experienced single episodes of hypocalcemia related to stressful events or infections, which required a temporary dose increase and additional calcium supplementation.

The older woman also experienced hypercalcemia 4.5 years after initiating the pump treatment. However, this was determined to be related to sarcoidosis, and the woman’s calcium levels were again restored after starting on prednisone treatment.

The continuous infusions were safe and the patients showed no changes in renal function, bone mass, or bone lesions over time.

Overall, the findings suggest that “in cases where even PTH injections do not allow sufficient disease control, long-term PTH pump therapy represents an alternative option, providing long-term stabilization of calcium and phosphate homeostasis,” the researchers concluded.