Beyond Calcium: A Holistic Approach to Optimizing Outcomes for Patients with Hypoparathyroidism

Chronic hypoparathyroidism (HypoPTH) is a rare endocrine disease with consequences across multiple organ systems, which makes it challenging to diagnose and manage. Conventional therapy for HypoPTH focuses on normalizing serum calcium levels and not treating the source, which is a lack of the parathyroid (PTH) hormone. HypoPTH results from insufficient levels of PTH and patients with this disease must be managed holistically, similar to how patients with other hormone deficiencies, such as diabetes, are treated. Just as people with diabetes are more than their HbA1c level, people living with chronic HypoPTH are more than their calcium levels.

HypoPTH is a hormone disorder

HypoPTH is a rare endocrine disease that results from the absence or deficiency of PTH, which is crucial for regulating calcium and phosphate levels in the body. While HypoPTH is frequently underdiagnosed, it is estimated that approximately 77,000 people are living with the disease in the United States. HypoPTH may result from surgery that damages the parathyroid glands, autoimmune/genetic causes, or may not have a known origin, such as idiopathic HypoPTH.

Insufficient parathyroid hormone leads to low levels of calcium and high levels of phosphate, which have significant effects on multiple organ systems. These effects may manifest as clinical symptoms (tingling/numbness, muscle cramps, seizures, wheezing, and irregular heartbeat), adverse health outcomes (kidney stones, kidney damage resulting in chronic kidney disease, cataracts, and basal ganglia calcifications), and decreased quality of life (due to fatigue, cognitive dysfunction, “brain fog,” and the challenge of managing symptoms and disease-related health issues).

Patients with HypoPTH experience the feeling that their symptoms and quality-of-life concerns are not being seen or heard by their healthcare providers when they address only the results of their blood tests and not the broader, negative impacts their hormone deficiency has on many aspects of daily living. These patients’ feelings are validated by several disturbing statistics from The Voices of HypoPARA 2.0, a recent patient survey conducted by the HypoPARAthyroidism Association.1

Two-thirds of respondents reported having at least one disease-related hospitalization before being diagnosed with HypoPTH, and most patients lived with symptoms of their disease for at least 6 months and, in some cases, more than 20 years before an accurate diagnosis. Even once diagnosed, only 25% of respondents strongly agreed that their physician fully understood their condition, and only 10% were happy with their treatment option.1

Additionally, 87% of respondents had developed HypoPTH following head or neck surgery (the most common cause of the disease), yet only 11% fully understood that this was a potential risk before they consented to surgery.1 This underscores the importance of hearing our patients and communicating with them more effectively, especially when a newly FDA-approved treatment option may help patients feel better and live more satisfying lives.

An evolving treatment landscape

Conventional therapy for HypoPTH typically involves the use of calcium supplements and vitamin D to raise serum calcium levels into the normal reference range. Some patients may also be given magnesium supplements and phosphate binders based on laboratory assessments of serum phosphate and magnesium levels. While these supplements can help to normalize blood chemistry, they are not entirely benign. When administered at the high doses needed in patients with HypoPTH, calcium supplementation can cause gastrointestinal side effects. When used long-term, they can also lead to chronic kidney disease and the development of calcifications in the kidneys, brain, and other organs.

In 2024, the US Food and Drug Administration (FDA) approved a new PTH hormone analog for the treatment of HypoPTH called palopegteriparatide (YORVIPATH). It is administered daily by subcutaneous injection.2 In an 82-patient randomized, double-blind, placebo-controlled Phase 3 clinical study, 79% of patients in the palopegteriparatide group met a 5-part efficacy assessment endpoint compared with 5% of patients in the placebo group.3 The 5-point efficacy assessment required that patients meet all of the following criteria at Week 263:

• Normalization of albumin-corrected serum calcium

• Independence from conventional therapy since Week 22 (that is, no active vitamin D and <600 mg/day of calcium supplementation)

• No increase in palopegteriparatide dose since Week 22

• No missing active vitamin D and calcium data since Week 22

• Palopegteriparatide dose of 30 mcg or less once daily during the 26-week treatment period

A collaborative approach to optimizing outcomes for patients with HypoPTH

Normalizing calcium is necessary but not sufficient to achieve optimal patient outcomes. Comprehensive and compassionate care of patients with HypoPTH must include consideration of physical, psychological, and quality-of-life factors in addition to calcium and phosphate levels. Achieving this holistic approach requires that HCPs work collaboratively with patients to understand the spectrum of symptoms they experience and how these symptoms impact their daily lives.

In my practice, I routinely ask specific questions to elucidate this rather than assuming that patients will recognize that what they are experiencing is related to their disease. In each interaction with one of my HypoPTH patients, I ask questions about:

• Physiologic aspects of the disease, including tingling/numbness, muscle cramps, seizures, wheezing, etc.

• Quality of life issues, including fatigue and brain fog.

• How they feel today compared with how they felt before disease onset.

• Anything they want to change about how their disease impacts their life.

Once I am fully informed about how each patient is experiencing HypoPTH, I can have a productive discussion about treatment options, including PTH hormone therapy, which allows the patient to make an informed decision about how they want to manage their disease.

Patient perspectives

One particular patient exemplifies how finding the right treatment can transform care. She is a 42-year-old woman who was very active and enjoyed surfing, running, and other activities as part of her daily routine. She developed HypoPTH after thyroid surgery, which significantly limited her ability to engage in these activities and other aspects of daily living. She required 4200 mg of calcium and 1 mcg of calcitriol daily to keep calcium between 8 and 8.5. Her calcium levels fluctuated with activity and illness, resulting in recurrent symptomatic hypocalcemia. She was no longer able to participate in any of her previous sports activities due to muscle cramping, fatigue and decreased sense of well-being.

She entered a clinical trial evaluating palopegteriparatide prior to its FDA approval and had a rapid and very positive response — so much so that she told me that she had “gotten her life back” and had been able to resume her previous activities.

Other patients have shared with me that they didn’t realize how poorly they had been feeling until they tried PTH replacement therapy. These patient stories are a compelling reminder that HCPs must remain up to date on the latest developments in HypoPTH diagnosis and treatment and empower patients to confidently advocate for the highest quality of care, fostering better health outcomes.

Now that we can address parathyroid deficiency rather than just calcium levels, treating our patients with HypoPTH will prove to be gratifying to both the provider and the patient. For me, being told that I helped someone “get their life back" never gets old.

References

1. The Voices of HypoPARA 2.0 Survey. Available at: https://www.hypopara.org/el-pfdd

2. YORVIPATH Prescribing Information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/216490s000lbl.pdf

3. Khan AA, et al. Efficacy and Safety of Parathyroid Hormone Replacement With TransCon PTH in Hypoparathyroidism: 26-Week Results From the Phase 3 PaTHway Trial. J Bone Miner Res. 2023 Jan;38(1):14-25. doi:10.1002/jbmr.4726