Chronic Hypoparathyroidism Today: Unmet Needs, Conventional Therapy Limits, and the Shift to PTH Replacement

Chronic hypoparathyroidism has historically been managed as a disorder of calcium deficiency rather than a true hormone deficiency, but this paradigm is changing. In this introductory segment of an HCPLive Special Report on the evolving landscape of hypoparathyroidism and the role of palopegteriparatide, Sara Lubitz, MD, explains that until 2015 hypoparathyroidism stood as the last major endocrine deficiency without an available hormone replacement. Since the advent of PTH-based therapies, clinical interest has grown in restoring more physiologic calcium homeostasis and mitigating the long-term complications associated with chronic disease.

Despite these advances, Lubitz notes that patients with chronic hypoparathyroidism continue to face substantial morbidity. She highlights increased risks of cardiac disease, kidney disease, cataracts, and hospitalizations, even among those receiving seemingly adequate therapy. Conventional regimens based on high-dose oral calcium and active vitamin D often produce wide fluctuations in serum calcium, excessive urinary calcium excretion, and calcium-phosphate imbalance, which can fuel nephrolithiasis, nephrocalcinosis, and chronic kidney disease. Importantly, neuromuscular and neurocognitive symptoms such as fatigue and “brain fog” frequently persist despite normal serum calcium on these regimens.

Lubitz underscores a persistent “empathy gap” between physician-reported and patient-reported outcomes, emphasizing that biochemical control alone does not equate to disease control from the patient’s perspective. She characterizes conventional calcium and vitamin D therapy as a work-around rather than true treatment of the underlying endocrine deficiency. This recognition has catalyzed a conceptual shift toward replacing the missing hormone itself. However, she notes that implementing PTH replacement has been technically challenging because of the naturally short half-life of PTH, a limitation that newer agents such as palopegteriparatide are specifically designed to address.