Parathyroid Allotransplant Transforms Life of Patient With Severe Hypoparathyroidism

Dawn Ethier, a police officer in Ottawa, Canada, recalls how her life revolved around managing her 100-pill-a-day regimen. Her symptoms began 3 weeks after her thyroid surgery, but it took another 4 to 5 months for her to be diagnosed with hypoparathyroidism.

Her life changed. "After about 2 years of struggling, I wasn't able to work because my symptoms were too unpredictable to allow me to do my job. It wasn't safe for the public, for my fellow officers, or for myself. My relationship with my children's father did not survive the stress of the constant worry about the future and my long absences from home due to hospital visits."

That's when she began researching options and found a study describing tissue implantation in Poland. Ethier brought that research to her doctor in Ottawa who reached out to Karen Devon, MD, MSc, assistant professor of surgery at the University of Toronto.

After reviewing the research, Devon became intrigued and eventually performed what may be the first parathyroid transplant of its kind in North America.

"To our knowledge, our patient is the first successful fresh normal-tissue parathyroid transplant from a deceased donor to a non-kidney transplant recipient in North America," Devon told Medscape Medical News in a phone interview.

Devon, an endocrine and thyroid surgeon at the University Health Network (UHN) in Toronto, and her surgical team presented the case in a poster at ENDO 2023, the annual meeting of the Endocrine Society, in Chicago.

She talked with Medscape Medical News about her patient's condition, the surgery, and its effects. Ethier explained how the surgery has transformed her life.

How did you become interested in Ethier's case?

This case fits perfectly well with my background. As an endocrine surgeon, I do a lot of thyroid and parathyroid surgery. Fortunately, UHN is a large, world-class transplant center, so I was able to assemble the team required to perform this surgery.

The patient, who had severe, disabling hypoparathyroidism, found me online while searching for someone who might do this surgery for her. After meeting with her, I became very interested in trying to help her, knowing that, if the surgery was successful, it may also help future patients. And when I asked our head of the transplant program, Dr Atul Humar, if doing this surgery would be feasible, he said he thought we have an obligation to try to help her.

I think this is an inspiring success story because it was patient initiated. We became very focused on this particular person so we could meet her specific needs and solve her serious problem.

What do parathyroid glands do?

Parathyroid glands are endocrine organs located beside the thyroid. Each normal gland is around the size of a grain of rice, and most people have four of them. Parathyroid glands produce parathyroid hormone (PTH), which controls calcium levels in the body. PTH regulates essential functions such as muscle and nerve function, as well as bone, cardiovascular, and mental health.

What is hypoparathyroidism and why is treating it so important?

Hypoparathyroid patients don't have enough parathyroid tissue to adequately regulate calcium, and their very low calcium can be difficult to treat. They may need supplementary calcium and other medications. Often their symptoms are not treated, so they have things like tingling in their extremities and on their face. In severe cases, they can have other problems like tetanus (lockjaw), cardiac issues, kidney stones, and calcifications elsewhere in the body. They may need multiple hospitalizations and need IV calcium treatment. It's often very much a quality-of-life issue.

Permanent hypoparathyroidism is usually a complication of thyroid surgery. Surgeons take care to avoid damaging the glands, but that's not always possible, and parathyroid gland damage is estimated to occur in 1% to 5% of total thyroidectomies.

Current treatments are limited, classically involving calcium and calcitriol, and more recently with recombinant PTH. Treating with recombinant PTH is expensive and requires multiple daily injections and monitoring. It may not control calcium levels and is not known to be suitable for long-term use.

Have parathyroid allotransplants been tried before?

Yes, but this is a pretty rare problem. The prevalence of hypoparathyroidism in the US is an estimated 37 per 100,000 people per year. But few patients have severe symptoms from it, and most cases can be controlled with calcium pills and other medications.

Since the first attempted parathyroid allotransplant in 1911, researchers have used cryopreserved, cultured, or hypercellular tissues to try to restore calcium homeostasis in patients with refractory hypoparathyroidism after thyroidectomy, without great success.

The most promising case, which my patient brought to me, was a patient in Germany in 2016 who had a parathyroid transplant from a living relative. That case led to our idea of taking a deceased donor's parathyroid, like you might take a kidney, liver, or other organ.

To our knowledge, our patient is the first successful fresh normal tissue parathyroid transplant from a deceased donor to a non-kidney transplant recipient in North America.

What were your patient's issues?

Our 43-year-old patient had undergone a total thyroidectomy for thyroid carcinoma in 2012. The surgery cured her cancer but left her with severe hypoparathyroidism. To manage her symptoms, she tried a range of therapies — hydrochlorothiazide, calcium, magnesium, calcitriol, vitamin D3, and a teriparatide continuous ambulatory delivery device (CADD) pump infusion. At one point, she was taking almost 100 pills per day.

Even so, she had severe refractory postoperative hypocalcemia with almost weekly ER visits for calcium infusions. Other problems included peripherally inserted central catheter (PICC)–line infection and sepsis, pulmonary embolism, and seizures, and she couldn't work or perform many other activities of daily life.

What did you and your team do?

This was our second transplant in this patient after an attempt in September 2021 that did not result in functioning parathyroid tissue.

Our standard transplant workup included cancer screening and pretransplant vaccines. And, of course, we discussed the risks for immunosuppression and other, unknown risks.

For the second try, in May 2022, when our organ procurement agency had a neurologically deceased donor available who was a good match, we drove to the site and retrieved four parathyroid glands from that donor and drove back to our center. About two and half hours later, we minced the parathyroids into small fragments and implanted them into several pockets we made in our patient's right brachioradialis muscle under sedation and local anesthesia. We gave her immunosuppressive medications — basiliximab induction, prednisone, tacrolimus, and mycophenolate — to prevent rejection, and she went home in 48 hours.

Nine days after our patient's surgery, her calcium and PTH levels rose, and by day 35, she remained on immunosuppressant drugs but was weaned off all calcium medications. At 1 year, she had no hypocalcemic symptoms, her PTH and calcium levels were normal, and she reported that she was thriving, with enough energy to spend time with her children, walk, and exercise.

What near- and long-term challenges might this patient expect?

We hope to study our patient's ongoing quality of life and needs by monitoring her future treatments, immunosuppressant drugs, precautions she may need to take, and care needs she may develop.

Why did the first attempt fail?

We reviewed the first attempt but did not come up with a good answer. Our original estimation of whether this would work was about 50-50. So, we were not very surprised that our first attempt failed, and that, when we tried again, we succeeded.

Why was finding an appropriate match difficult?

The ease of matching depends on how many antibodies to other people's tissues you have. People with more antibodies, like our patient, have a very high panel reactive antibody (PRA) number and are more difficult to match. We expected only about 2% of available donors to be a good match for her, so we knew we might have a long wait.

Why is ischemic time important, and how does it play out in this case?

People have studied the amount of time various organs can be ischemic and still be viable, but we don't have that information for parathyroids. We often implant parathyroids up to 3 hours after they've been removed from a patient during their own thyroidectomy. Maybe we can extend that time, but we don't yet know, and more research is needed.

What future research are you and your colleagues planning?

We plan to do more of these transplants, and we expect researchers in other centers, using different protocols, to study different aspects of this procedure.

We have many unanswered questions — for example, exactly what makes a patient reject their transplant? — and we hope that doing more of these cases will help answer them.

I hope we'll learn about how to increase this procedure's success, in particular how much immunosuppression is really necessary to have a successful transplant.

How can doctors help their patients get involved with your ongoing research?

We are recruiting patients to investigate whether deceased donor parathyroid allotransplant and immunosuppression is safe and effective for patients with severe refractory hypoparathyroidism following thyroidectomy. For more information about this study, or if you have patients who might benefit from participating in it, go here.

The Patient's Perspective: Not Another Dead End

Dawn Ethier says her life was transformed following the parathyroid transplant. She shares her story here and relays how, after first connecting with Dr Devon, she waited for a donor.

When you learned that a transplant was available, what did you think? How did you feel?

I expected it to be another dead end. However, not taking that road would have made me feel like I was giving up. And if I had allowed myself to give up hope, I wouldn't be here today. During the process, I felt neutral about it until I got the first call.

 

You needed to be available to drive several hours from Ottawa to Toronto on short notice. Were you always "on call" in case donor organs would become available?

From the moment I was listed, I was glued to my phone and stayed ready to leave at any moment.

When you learned that donor organs were available, how much lead time did you have to get to the hospital for your surgery?

The first transplant was very fast: They phoned and told me to come to Toronto ASAP. But the second time was much more relaxed. They called me 24 hours beforehand to let me know there was a possible match and that they would call back when they wanted me to start driving to Toronto.

How long did the surgery take? Did you have any complications? How soon did you go home? Did you have any problems afterwards?

The surgery took a little time, maybe 45 minutes to an hour. I had a hard time transitioning onto the immunosuppressants, but the transplant caused me no issues.

What treatments are you on now?

I am on three different types of immunosuppressants, for life, and a few medications to counteract their side effects.

How has the surgery changed specific aspects of your life?

The surgery has given me freedom. It has freed me from the psychological anxiety that such an unmanaged illness can cause. I have the freedom to explore my authentic self and find out what truly excites and pleases me. I lost who I was for so many years. Now, I feel like I am getting to know who I truly am.

One example is that muscle cramping used to make walking difficult. But now, I take long walks with my husband and the dogs. And I have even started running again.

Going forward, will you need to take any special precautions?

My immune system is fragile due to the antirejection medications, so I need to be vigilant about the spread of germs. I also need to avoid the sun without sunscreen.

What advice do you have for other people who may have similar health challenges?

You need to get as invested in your health as much as you expect your doctor to. Doctors have a multitude of patients, a home life, and their own struggles. They can only work so much on one case, and we are responsible for our own health. Researching and communicating effectively with your primary care physicians is a must.

Devon and Ethier did not report any relevant financial relationships.

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Credits:
Lead image: Kateryna Kon | Dreamstime.com
Image 1: Dawn Ethier
Image 2: University Health Network

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Cite this: Parathyroid Allotransplant Transforms Life of Patient With Severe Hypoparathyroidism - Medscape - Jul 25, 2023.