What is Hypoparathyroidism?

Hypoparathyroidism is a condition where your body doesn’t produce enough parathyroid hormone (PTH) or the hormone doesn’t work properly. This hormone normally helps keep your calcium levels in balance. When it’s missing or not working well, you can have low calcium levels, high phosphate levels, and sometimes too much calcium in your urine. These changes can affect many parts of your body, potentially causing problems with your kidneys, bones, heart, and nervous system.

What Causes Hypoparathyroidism?

Surgery, particularly thyroidectomy or parathyroidectomy, accounts for 75–80% of all hypoparathyroid cases. Non-surgical causes account for 20-25% of cases and include autoimmune conditions (i.e. autoimmune polyendocrine syndrome type 1), genetic syndromes (i.e. DiGeorge syndrome and autosomal dominant hypocalcaemia), infiltrative diseases (i.e. hemochromatosis and Wilson’s disease), and magnesium disorders.

How is it diagnosed?

Diagnosis relies on the confirmation of low calcium levels with inappropriately low or normal PTH levels. Other tests that are markers of the disease can include high serum phosphate, low 1,25-dihydroxyvitamin D, and elevated calcium levels in the urine. Patients who develop hypoparathyroidism after surgery can have transient or permanent disease.

What Complications Can It Cause?

The complications of hypoparathyroidism are wide-ranging and affect multiple system:

• Kidneys: Too much calcium in your urine can lead to kidney stones, calcium deposits in the kidneys, or even kidney damage.
• Bones: Dysregulation in how your bones remodel and repair can occur.
• Heart: Low calcium levels can lead to changes in heart rhythm (arrhythmias) and other heart-related issues such as cardiomyopathy.
• Nervous System: Low calcium can cause muscle cramps, spasms, seizures, and even changes in the brain such as calcifications in the basal ganglia.
• Immune System: Calcium plays a role in how your immune cells work, so you might be more prone to infections.

How Is It Treated?

A. Conventional Therapy

The standard treatment is to take oral calcium and activated forms of vitamin D (i.e. calcitriol) to increase calcium levels in the body. The goal is to keep your blood calcium levels at the lower end of the normal range. This approach helps reduce risks like kidney stones. However, calcium and activated vitamin D supplements can sometimes lead to fluctuations in calcium levels, a need for many pills, high urinary calcium, increased phosphate levels and decreased quality of life.

B. PTH Replacement Therapy

PTH replacement offers a more physiological approach to managing hypoparathyroidism, reducing the need for calcium and vitamin D supplements and improving quality of life.

• • PTH (1-34): This active fragment of PTH is effective to keep calcium levels normal, reduce urinary calcium levels, and may improve bone strength. However, because it doesn’t last very long in the body, it must be given several times a day or through a continuous pump.   PTH(1-34) is not an approved therapy for patients with hypoparathyroidism but is used off-label for this indication.
  • PTH (1-84): With a longer half-life, this molecule last longer than PTH (1-34) and can be administered once daily. Clinical trials have shown its efficacy in reducing calcium and vitamin D supplementation requirements while maintaining normal calcium levels in the blood. Unfortunately, production of this form was being phased out globally since the end of 2024 due to manufacturing challenges.
  • Palopegteriparatide (TransCon PTH): This is a newer treatment that links a fragment of PTH (1-34) to another molecule to extend its action profile over a longer time period.  Recent studies have shown that it effectively keeps calcium levels normal, reduces urinary calcium, reduces phosphate levels, improves renal function and quality of life. Many patients using this treatment no longer need conventional therapies. The FDA approved this treatment for hypoparathyroidism in 2024.

C. Emerging Therapies

Emerging treatments aim to address the limitations of conventional and current PTH replacement therapies:

• • • Eneboparatide: A long-acting PTH/PTHrP currently in advanced clinical trials. Early results from these studies are promising for both maintaining calcium balance and bone health.
    • Calcilytics (Encaleret): These drugs modulate the calcium-sensing receptor to increase PTH secretion. They are also under investigation in advanced clinical trials at this time.

Summary

The management of hypoparathyroidism has evolved significantly, with more recent therapies offering improved outcomes compared to conventional treatment. While challenges remain in addressing complications and optimizing long-term care, ongoing research and innovation are paving the way for more effective, patient-centered solutions.

 

Written by Sarah Khan MD FRCPC, Staff Endocrinologist, Bone and Research Education Clinic, Oakville ON, January 2025.