Andrea Ferenczi, MD, FACE, ECNU 

In this episode, Dr. Cusano asks Dr. Khosravi to identify the most significant unmet needs remaining in the current treatment landscape for hypoparathyroidism.

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.

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In this episode, Dr. Cusano asks Dr. Andrea Ferenczi to describe how hypoparathyroidism management must be adapted for special populations, including children, older adults, and those with significant comorbidities.

Hypoparathyroidism in Special Populations: Pediatric, Geriatric, and Comorbid Patients

For pediatric patients, Dr. Ferenczi explains that the key adaptations involve growth considerations, dosing logistics, and a more conservative stance toward PTH therapy. Active vitamin D—specifically calcitriol—is the treatment backbone, bypassing the renal 1-alpha-hydroxylase step that is impaired by PTH deficiency. Calcium is weaned to the minimum needed to maintain low-normal serum levels, with divided doses under 500 mg at mealtimes to optimize absorption. Neonatal hypocalcemia may be managed with low-phosphate formulas to optimize the calcium-to-phosphate ratio. PTH analogs are not standard of care in children, are currently only adult-indicated, and pediatric registration studies are just beginning. She highlights that non-surgical genetic causes—APS1, DiGeorge syndrome, ADH1—predominate in pediatrics and require syndrome-specific surveillance for associated complications such as deafness, cardiac disease, and immune deficiency.

For geriatric and comorbid patients, Dr. Ferenczi notes that management divergences are driven largely by comorbidity burden rather than age alone. Declining GFR from CKD narrows the already tight therapeutic window by impairing vitamin D activation and phosphate clearance, raising calcium-phosphate product risk, and creating a strong rationale for PTH replacement. Osteoporosis may benefit from PTH therapy's bone anabolic properties, though bisphosphonates and denosumab can precipitate significant hypocalcemia and require careful monitoring. Cardiovascular disease and polypharmacy in older patients increase the risk of QT prolongation and arrhythmias from calcium swings. Patients with malabsorption—from bariatric surgery, IBD, or proton pump inhibitor use—should receive calcium citrate over carbonate and represent a recognized trigger to consider PTH replacement.

In the next episode, "Unmet Needs in the Hypoparathyroidism Treatment Landscape," Dr. Khosravi surveys the most significant remaining unmet needs in hypoparathyroidism—from the limitations of conventional and PTH replacement therapy to data gaps in special populations, skeletal outcomes, and the ongoing burden experienced by patients.

In this episode, Dr. Cusano asks Dr. Sara Lubitz to address management of hypoparathyroidism in pregnant and postpartum patients.

Hypoparathyroidism Management During Pregnancy and Breastfeeding

Dr. Lubitz explains that pregnancy significantly alters calcium physiology. PTHrP produced by the placenta and the lactating breast, combined with increased 1,25-dihydroxyvitamin D in the first trimester, can dramatically shift the doses of active vitamin D and calcium required. This variability is unpredictable—some patients need significantly higher doses during pregnancy while others need lower doses. Poor maternal calcium control carries serious risks including premature labor, premature rupture of membranes, preeclampsia, seizures, kidney stones, and arrhythmia. Fetal risks include low birth weight and fetal seizures. If maternal calcium is too high, the fetus may develop hypoparathyroidism; too low, the neonate risks hyperparathyroidism.

Current guidelines recommend checking calcium, magnesium, phosphorus, and renal function every two to four weeks throughout pregnancy, with additional checks within one week of any dose adjustment.

For preconception counseling, Dr. Lubitz emphasizes preparing patients for significant calcium fluctuations during pregnancy and breastfeeding, including the frequently overlooked transition point when breastfeeding ends—a time when calcium metabolism can shift abruptly. She notes that all women of childbearing age should be informed there are no safety data for PTH analogs in pregnancy or breastfeeding, and that guidelines recommend switching back to conventional therapy as part of preconception planning.

Dr. Cusano shares a case in which a patient planned to continue PTH 1–84 during a second pregnancy but was forced to transition mid-pregnancy due to a product recall, fortunately without safety concerns. Dr. Shoback confirms she has not yet used PTH analogs in pregnant patients. The panel agrees that real-world data from registries—including the Paradigm Registry and the Global Pregnancy Registry for palopegteriparatide—are urgently needed to guide clinical practice for this population.

In the next episode, "Hypoparathyroidism in Special Populations: Pediatric, Geriatric, and Comorbid Patients," Dr. Ferenczi outlines how hypoparathyroidism management must be adapted for children, older adults, and patients with renal impairment, malabsorption, cardiovascular disease, and other complex comorbidities.

In this episode, Dr. Cusano asks Dr. Khosravi to explain how multisystem complications beyond renal disease factor into treatment selection and monitoring in hypoparathyroidism.

Multisystem Complications: Guiding Treatment Selection in Hypoparathyroidism

Dr. Khosravi frames her response around the wide spectrum of disease severity. At the mild end, patients may be successfully managed with conventional calcium and active vitamin D therapy. As the number and severity of complications increase, conventional therapy becomes increasingly insufficient.

She explains that some complications, such as neuromuscular irritability and QTc prolongation, are driven primarily by hypocalcemia and may respond to dose adjustment of calcium, active vitamin D, or magnesium supplementation. Phosphorus management presents a more difficult challenge on conventional therapy: reducing calcitriol doses to control hyperphosphatemia can worsen hypocalcemia, and a low-phosphate diet is difficult to implement consistently since high-phosphate foods such as dairy also contain calcium.

Basal ganglia calcifications and extraskeletal calcifications appear driven partly by chronically elevated phosphate levels and are unlikely to reverse once established, regardless of whether treatment is intensified or transitioned to PTH replacement. Similarly, ophthalmic complications such as cataracts, most common in non-surgical hypoparathyroidism, are not expected to reverse with treatment. Cardiovascular complications driven by hypocalcemia—such as arrhythmias—may improve with calcium correction, but hyperphosphatemia-related vascular and valvular calcification requires PTH replacement to adequately address.

On skeletal outcomes, Dr. Khosravi reiterates that while bone density typically moves toward more normal ranges with PTH replacement, long-term fracture risk data comparing PTH replacement to conventional therapy remain lacking. She identifies quality of life as the most compelling current indication for PTH replacement, noting that clinical trials have demonstrated clear and sustained quality-of-life improvements. For patients whose primary burden is reduced quality of life, she characterizes PTH replacement as clearly the better choice.

In the next episode, "Hypoparathyroidism Management During Pregnancy and Breastfeeding," Dr. Lubitz navigates the complex calcium physiology of pregnancy and breastfeeding in patients with hypoparathyroidism, covering monitoring frequency, dose adjustments, preconception counseling, and the current limitations of PTH analog use in this setting.

Andrea Ferenczi, MD, FACE, ECNU

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