Managing Renal Function and Serum Calcium in Hypoparathyroidism, With Mishaela Rubin, MD, MS

Published in October 2025, a new set of best practice recommendations for the treatment of hypoparathyroidism (HypoPT) has updated the existing 2022 international guidelines by incorporating therapeutics from the past 3 years, including the recently approved molecule palopegteriparatide.1

HypoPT is a metabolic disorder occurring as a result of hypocalcemia and hyperphosphatemia, which are in turn caused by either a failure of the parathyroid glands to secrete sufficient amounts of active PTH or an inability of PTH to induce a biological response in target tissues. 75% of all cases are caused by surgery, but nonsurgical causes can include autoimmune, genetic variants, metastatic, and radiation.2

These updated best practice statements were drafted by a team of international HypoPT experts and resulted from an initiative launched by the Canadian Society of Endocrinology and Metabolism (CSEM) in partnership with several other international endocrine societies. The document aims to provide a practical framework to guide PTH replacement therapy usage with palopegteriparatide in chronic HypoPT.1

The HCPLive editorial team sat down with Mishaela Rubin, MD, MS, professor of medicine at Columbia University Irving Medical Center and a contributing author to the new recommendations, to discuss her thoughts on optimal HypoPT care, including postsurgical risk assessment, genetic evaluation, and dose titration of parathyroid hormone (PTH) therapies.

“I think that clinicians who aren’t sensitized or aren’t aware of hypoparathyroidism might not think about lab results that might be suggestive or what they might mean,” Rubin told HCPLive. “I oftentimes see patients who’ve had symptoms and been seen by different doctors, but nobody made the diagnosis.”

The recommendations open by covering challenges presented by HypoPT, both in diagnosis and treatment. In addition to the disease’s own effects, conventional therapies, such as oral calcium supplements, can potentially increase serum phosphorus, hypercalciuria, and hypercalcemia, and could contribute to renal function declines.1

The document goes on to establish optimal uptake and dose titration for PTH and PTH analogues, emphasizing its proven efficacy in reducing urine calcium excretion and maintaining eucalcemia. Ultimately, however, the recommendations shift to palopegteriparatide, a recently approved treatment consisting of PTH (1-34) linked to a polyethylene glycol moiety. With a half-life of roughly 60 hours and providing a sustained release of active PTH, palopegteriparatide allowed patients in multiple phase 2 and 3 trials to achieve total independence from conventional therapy.1

The guidelines then turn to emerging therapies, such as eneboparatide, which is a long-acting PTH/PTHrP analog with evidence for lowering urine calcium, normalizing bone remodeling, and achieving eucalcemia. Eneboparatide has received fast track designation from the US Food and Drug Administration (FDA) and is currently under investigation in phase 3 clinical trials.1

Ultimately, the guideline encourages close monitoring of serum calcium and renal function, outlining the risks and benefits of each potential therapy and highlighting potential upcoming treatments. The document also emphasizes that updates are expected in 5 years, provided that further long-term data is made available.1

“The most important medical complication, I would say, is renal,” Rubin said. “Patients should have some type of renal imaging, at least at baseline, whether that’s a renal ultrasound or a CT scan, to look for nephrocalcinosis and nephrolithiasis. We worry about their hypocalcemic symptoms, about their struggles with neurocognitive function, but I think that careful renal screening sometimes falls under the radar.”

Editor’s Note: Rubin reports disclosures with Amgen, Ascendis, Radius, and NPS Pharmaceutical/Shire.

References

1. Khan AA, Ali DS, Bilezikian JP, et al. Best practice recommendations for the diagnosis and management of hypoparathyroidism. Metabolism. 2025;171:156335. doi:10.1016/j.metabol.2025.156335

2. Hakami Y, Khan A. Hypoparathyroidism. Front Horm Res. 2019;51:109-126. https://pubmed.ncbi.nlm.nih.gov/30641528/