Unmet Needs in the Hypoparathyroidism Treatment Landscape

Dr. Khosravi provides a wide-ranging assessment. On the conventional therapy side, key limitations include failure to fully normalize mineral homeostasis in a meaningful proportion of patients—particularly an inability to adequately address hypercalciuria and lower phosphorus—persistence of low bone turnover, irreversibility of some complications once established, and ongoing calcium fluctuations that cause harm. Quality of life remains unaddressed for many patients. Surveys across countries indicate that up to 80% of patients report an empathy gap on the part of their providers in understanding the true burden of disease—including the daily pill burden of conventional therapy.

Disparities and inconsistencies in complication data between surgical and non-surgical hypoparathyroidism also represent a significant unmet need; better long-term evidence is needed to clarify these differences.

On the PTH replacement side, palopegteriparatide represents a major advance, but still requires a daily injection. Patients would clearly prefer a non-injectable or less-frequent option. Fixed daily dosing also cannot replicate the minute-to-minute calcium homeostasis provided by endogenous PTH. Special populations—pregnant and lactating women and children—remain largely without robust evidence-based guidance, and existing recommendations for these groups are largely extrapolated from other populations.

Long-term skeletal data represent perhaps the most important unanswered question: whether PTH replacement reduces fracture risk compared to conventional therapy remains unknown. Dr. Khosravi also looks forward to advances in surgical parathyroid identification techniques such as autofluorescence, potential cell-based therapies, point-of-care calcium monitoring, precision therapies such as encaleret for ADH1, and the maturation of real-world registry data.

In the next episode, "Communicating the Multisystem Nature of Hypoparathyroidism to Patients," Dr. Ferenczi shares practical strategies for helping patients understand why lifelong multisystem monitoring is necessary even when they feel well, and explains how to engage patients as active partners in managing their chronic disease.