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Addressing Treatment Needs in ADH1
Addressing Treatment Needs in ADH1: Patient Perspectives and Expert Insights

Released: July 29, 2026

Geena DellaFiore
Geena DellaFiore
Michael Mannstadt
Michael Mannstadt, MD
Mark L. Warren
Mark L. Warren, MD, FACE
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Key Takeaways
  • ADH1 is frequently underrecognized and can take years to diagnose because of variable symptoms, including hypocalcemia, seizures, fatigue, anxiety, and cognitive changes, and limited healthcare professional awareness of ADH1 as a potential cause of idiopathic hypoparathyroidism.
  • Genetic testing is essential for confirming ADH1, and family testing can identify at-risk family members, who may benefit from appropriate monitoring and management, as well as family members who do not carry an altered gene.
  • Encaleret is an emerging therapy that specifically addresses the underlying pathophysiology of ADH1 by targeting the calcium-sensing receptor (CaSR), and it has the potential to correct mineral metabolism and reduce treatment burden.

In this commentary, experts provide clinical insights into patient perspectives on disease recognition, genetic testing, and emerging therapeutic approaches to improve the care of patients with autosomal dominant hypocalcemia type 1 (ADH1).

Improving Recognition of ADH1 as a Possible Cause of Hypoparathyroidism

Patient Perspective:
I experienced my first ADH1 symptom as an adult. I was 20 years of age when I lost consciousness because of hypocalcemia, and I was hospitalized for a week. After that first incident with hypocalcemia, I was able to go several years without taking any medication, and I was not symptomatic. It was only as I started getting into my early 30s that symptoms really started to ramp up, and I was experiencing heart palpitations, numbness and tingling in my hands, brain fog, extreme anxiety and extreme fatigue, and just an overall sense of not feeling like myself.

I was given 2 diagnoses prior to being diagnosed with ADH1. I was told I had hypocalcemia for several years and then was finally diagnosed with idiopathic hypoparathyroidism in my early 30s. It took me more than 20 years to get a confirmed diagnosis of ADH1.

Michael Mannstadt, MD:
Patients with ADH1 can present with a wide range of symptoms. Among the most serious are seizures, which may involve loss of consciousness. Seizures are not uncommon as the first sign of ADH1 and can be frightening and even life-threatening, depending on the circumstances. Numbness and tingling in the hands are common symptoms of hypocalcemia and are frequently seen in ADH1. Other symptoms of hypoparathyroidism that may occur in ADH1 include heart palpitations, anxiety, severe fatigue, a general feeling of not being oneself, and cognitive difficulties, often described as “brain fog.”

Because ADH1 presentation is variable, improving diagnosis begins with recognizing that ADH1 is a genetic form of hypoparathyroidism marked by low parathyroid hormone (PTH) levels and hypocalcemia. Diagnosis of hypoparathyroidism may be delayed because calcium abnormalities are overlooked. Features that should raise suspicion for ADH1 include young age at presentation, seizures as the first symptom, hypoparathyroidism without a clear cause (idiopathic hypoparathyroidism), and a family history of the condition, as ADH1 is one of the most common genetic forms of hypoparathyroidism.

Mark L. Warren, MD, FACE:
If ADH1, or another genetic form of hypoparathyroidism, is suspected, healthcare professionals (HCPs) should be prepared to order genetic testing. Test kits can be ordered online at no charge through sponsored programs, and sample collection is relatively easy, typically involving a cheek swab or blood sample.

Interpreting Genetic Testing Results

Patient Perspective:
When I started the process for genetic testing, I made an appointment with a genetic counsellor, and we discussed my medical history, my family history, and she went over hypoparathyroidism as a whole. She discussed the testing procedure, and she also discussed the possible test results, which were positive, negative, and incidental findings. She went into more detail about incidental findings because she told me that they were testing for 26 hypoparathyroidism genes that they were aware of, but there could be other genes that they were not aware of and that they could not test.

Michael Mannstadt, MD:
It is important that a genetic counselor, or HCP ordering the test, explains the purpose of genetic testing and obtains informed consent beforehand. Preparing patients for the types of results they may receive can help reduce confusion. Outcomes might not be definitive. For example, testing may identify a variant of uncertain significance (VUS). A VUS is a change in the DNA that is not yet understood well enough to classify as disease-causing or harmless. Although many genetic variants associated with ADH1 have been identified, knowing the specific variant is not always helpful for predicting disease severity or prognosis. More information about ADH1 variants can be found online (https://casrdb.mgh.harvard.edu/).

Role of Family Testing in ADH1 Diagnosis

Patient Perspective:
After I received my positive ADH1 genetic result, I had a follow-up call with a genetic counsellor. She went over the result and mentioned that I should be sharing this with my healthcare team. She mentioned that my immediate family should be tested and that either one of my parents had a 50% chance of carrying the genetic mutation, and I would be provided with a family communication letter that I could share with them. I knew that my family had to get tested. The HypoPARAthyroidism Association held a family genetic testing event in my home state, where all my family was able to come and get tested very easily.

Mark L. Warren, MD, FACE:
Inheritance of ADH1 is autosomal dominant, meaning offspring of individuals who have a variant that causes ADH1 will have a 50% chance of inheriting ADH1. Genetic testing plays an important role in genetic counseling because it provides families with information on inheritance risk so they can make informed decisions. It may also help patients access appropriate therapies as they become available.

Michael Mannstadt, MD
Genetic testing provides a definitive diagnosis by confirming whether an individual has inherited an ADH1-associated variant. This paves the way for the person to receive appropriate monitoring, including regular assessment of calcium levels and other biochemical markers, to recognize when treatment is needed.

The HypoPARAthyroidism Association hosts family testing events, where relatives of affected individuals can receive education about ADH1, undergo genetic testing, and connect with others facing similar experiences. These events, along with patient organizations, provide valuable education, emotional support, and opportunities to share experiences while also serving as resources for HCPs and researchers.

Need for Additional Therapies for ADH1

Patient Perspective:
When I first got diagnosed with idiopathic hypoparathyroidism, I was started on calcium supplements and active vitamin D. That was a big challenge for me. I had to take a lot of medication, and it was barely keeping my calcium levels stable. I experienced extreme fatigue during this time, and I was not feeling like myself. I had little energy, and I had really bad anxiety. The constant changes in the oral medication made me feel just awful almost every day.

Then when I learned there was a PTH therapy that was about to be approved, I had a lot of hope that I was going to be feeling better, and it was going to be the magic answer for me. I started on the PTH therapy and I felt great for a little while. Until I had to have constant adjustments, my calcium levels kept dropping and I was still symptomatic every week. I would experience anxiety, fatigue, and brain fog, and it was challenging to get through my weeks. Still to this day, I am experiencing symptoms that affect my weeks on PTH therapy and going through constant dose changes.

An ideal treatment for me would bring me consistency, not just in my lab values, but in how I feel day to day. It would bring me stability in my calcium levels without constant adjustments or fear of sudden symptoms.

Michael Mannstadt, MD
Conventional treatment for hypoparathyroidism consists of calcium supplements and active vitamin D (calcitriol), which raise blood calcium levels and reduce the risk of symptoms. Although effective, this approach is not satisfactory and does not address the underlying cause of the disease. Calcium levels may remain variable, and treatment can increase urinary calcium excretion, raising the risk of long-term kidney complications in people with ADH1. PTH replacement therapy has also been approved to treat hypoparathyroidism, but it does not directly address the underlying cause of ADH1.

Fortunately, newer therapies are changing the treatment landscape. The ideal treatment is one that targets the underlying cause of ADH1: the altered calcium-sensing receptor (CaSR). The investigational agent encaleret has been developed to normalize the function of the CaSR. It not only increases PTH levels, but also reduces urinary calcium excretion through PTH action and also by normalizing the function of the CaSR in the kidneys, allowing patients to discontinue calcium and calcitriol. It is also administered as an oral tablet rather than an injection, offering a more convenient treatment option for patients. Initial data supporting encaleret safety and efficacy were published in a phase II clinical trial (NCT04581629), and CALIBRATE (NCT05680818) is global phase III clinical trial comparing encaleret vs conventional care for patients with ADH1.

Mark L. Warren, MD, FACE:
Palopegteriparatide, a PTH analog approved by the FDA for hypoparathyroidism, is currently the most specific treatment available for ADH1. However, encaleret, which is an investigational therapy that specifically targets the underlying causes of ADH1, is expected to normalize calcium and parathyroid hormone levels, resolve excess calcium urinary excretion, and allow patients to discontinue calcium and calcitriol. Of note, encaleret has been accepted by the FDA for review with an anticipated decision in May 2027.

Summary
Diagnosing and managing ADH1 can be challenging. HCPs should be aware of clinical presentations that suggest the possibility of ADH1 and use genetic testing, which is available at no cost, to confirm the diagnosis. Emerging therapies target the underlying mechanism of ADH1, with the goal of improving calcium regulation, reducing treatment burden, and enhancing patient outcomes.

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