Both Ends of the Spectrum: Diagnosing, Examining, and Treating Hypoparathyroidism and Hyperparathyroidism Patients

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Next month’s Endocrine Society Clinical Endocrinology Update 2022 will offer attendees a variety of courses on the latest diagnosis and treatment recommendations for several endocrine conditions. Aliya Khan, MD, FRCP, FACP, talks to Endocrine News about her session, “Diagnosis and Management of Hyperparathyroidism & Hypoparathyroidism,” recent breakthroughs, what attendees can expect, and the “good news” she’ll be sharing.

During the course of a Phase 3 trial investigating a potential drug to treat adults with hypoparathyroidism, Aliya Khan, MD, FRCP, FACP, FACE, professor of Clinical Medicine at McMaster University in Ontario, Canada, had a patient who was an operating room nurse who had a total thyroidectomy and developed hypoparathyroidism. The patient couldn’t think clearly – thoughts so muddied, in fact, that she had to quit her job and go on disability. “And then after we started on this study,” Khan says, “she was actually able to go back to work. She came in crying and said, ‘Dr. Khan, you gave me my life back!’”

Data from this trial – looking at the efficacy and safety of an investigational prodrug of parathyroid hormone (PTH) in development as a once-daily hormone replacement therapy – were presented at ENDO 2022 in Atlanta in June. (Ascendis funded the trial and is marketing the drug as TransCon PTH).

Next month, at Clinical Endocrinology Update (CEU), Khan will speak about this drug and other new molecules in development for the treatment of hypoparathyroidism. Her talk, titled “Diagnosis and Management of Hyperparathyroidism & Hypoparathyroidism,” as its name suggests, will look at complications of the parathyroid glands from both ends of the calcium spectrum – how to evaluate and prevent the short-term and long-term complications of hypoparathyroidism, and how and when to use PTH replacement therapy.

Khan will also go over how to diagnose hyperparathyroidism and give an overview of its complications, as well as suggest when to operate and when to use medical management. “I will also be presenting on the diagnosis and management of parathyroid disease in pregnancy,” she says. “In addition, I will provide an overview of the new global guidelines on both hypoparathyroidism as well as primary hyperparathyroidism.”

Detailed Assessment

One of the learning objectives for this CEU presentation is to identify updated approaches to patients with normocalcemic hyperparathyroidism. Khan explains that in these patients, it is critical to exclude a physiologic rise in PTH which can occur in the presence of a normal serum calcium. This is often due to a number of conditions: vitamin D insufficiency or inadequate calcium intake or absorption; chronic kidney disease; or other drugs which can elevate serum PTH without elevating serum calcium, such as antiresorptive therapy (denosumab or bisphosphonates), hydrochlorothiazide, or lithium.

“We want to improve patients’ wellbeing from day to day, and we can normalize calcium with calcium and active vitamin D, but we’re not helping the long-term complications with conventional therapy. And if we’re making that likelihood of chronic kidney disease earlier and more severe, then we’re not really helping our patients.”

Aliya Khan, MD, FRCP, FACP, FACE, professor, Clinical Medicine, McMaster University, Ontario, Canada

“Even other diseases such as Paget’s disease or hypercalciuria can result in a physiologic rise in PTH, and these conditions need to be excluded before a diagnosis of normocalcemic hyperparathyroidism can be confirmed,” Khan says. “A detailed assessment will be very helpful in evaluating the underlying condition and making the correct diagnosis.”

Misreading Symptoms

Indeed, both diseases can be debilitating, and cause a wide variety of symptoms that can diminish a patient’s quality of life. And they can go overlooked by providers who chalk the initial symptoms up to anxiety and stress. Khan tells Endocrine News that in hypoparathyroidism, while about 75% of cases are in patients who are postsurgical (like the O.R. nurse above), the rest are due to autoimmune diseases or genetic causes, and a primary care physician might not check those patients’ serum calcium levels. “So, if [the patients] are confused or they’re having anxiety or numbness or tingling, and if it’s a young woman, [the physicians] will say, ‘Oh, you’re just anxious. There’s nothing,’” she says.

Khan goes on to say that patients who have non-surgical hypoparathyroidism will often present with something catastrophic, like a seizure, because their calcium keeps dropping but a diagnosis is never made because those levels weren’t checked. “We really want to emphasize: check calcium, correct for an albumin, check PTH. And if both of them are low, or the PTH is inappropriately in the normal range, then look for hypoparathyroidism, confirm the diagnosis,” she says. “And if it’s not postsurgical, then we gave a very nice strategy in the guidelines that we presented as to how to find what the underlying causes for the hypoparathyroidism.”

Changing Patients’ Lives

And once that diagnosis of hypoparathyroidism is finally made, for now, these patients are treated with active vitamin D and calcium, but that treatment can increase the risk of long-term complications because it can further elevate phosphate, which can cause calcium and phosphate to deposit in the brain, behind the eyes, and in the kidneys, which can cause nephrocalcinosis, with the whole renal parenchymal calcifying.

Khan says that during her CEU talk, she will provide an update on all the new advances in drug therapy for hypoparathyroidism. She points to the aforementioned study of the PTH prodrug, as the investigators were able to show a consistent decline in urine calcium, as well as reductions in phosphate. “[The study] also showed significant improvements in quality of life while maintaining a normal calcium and stopping calcium and active vitamin D,” she says. “We want to improve patients’ wellbeing from day to day, and we can normalize calcium with calcium and active vitamin D, but we’re not helping the long-term complications with conventional therapy. And if we’re making that likelihood of chronic kidney disease earlier and more severe, then we’re not really helping our patients.”

And it wasn’t just the patient who was returned to work as a nurse in the operating room who benefitted from these new treatments for hypoparathyroidism. Other patients got raises at their jobs or were able to go back to school to finish their degrees. “It’s changing people’s lives,” Khan says. “One guy always wanted to do construction, but that requires a lot of calcium because it’s heavy, physical duty, and he was on disability sitting at home. Now he’s building houses. He comes in sweating, he’s really into it. And we say, ‘What are you doing?’ He says, ‘Oh, I’m building my fifth house.’”

“It’s really nice to be able to have such a big impact because there’re not that many areas in medicine where we can make a huge change in quality of life and turn people’s life around,” she continues, “but in hypoparathyroidism we’ve been able to demonstrate that and it’s really a very rewarding study to be a part of.”

Bearing Good News

Khan says she’s excited about these new molecules for the treatment of hypoparathyroidism that are in development. She says that they include different formulations of PTH that have a longer half-life than teriparatide (which is only one hour). “rhPTH 1-84 has a three-hour half-life and TransCon PTH has a 60-hour half-life and provides stability in serum calcium in addition to lowering serum phosphate, and urine calcium and improving quality of life,” she says.

“[Attendees] will be treated to a state-of-the-art lecture providing an overview of both primary hyperparathyroidism as well as hypoparathyroidism, summarizing advances in knowledge on how to diagnose and treat these conditions. Key recommendations from the upcoming global guidelines will also be presented.”

Aliya Khan, MD, FRCP, FACP, FACE, professor, Clinical Medicine, McMaster University, Ontario, Canada

And she says she’s eager to bring the good news to CEU next month. “[Attendees] will be treated to a state-of-the-art lecture providing an overview of both primary hyperparathyroidism as well as hypoparathyroidism, summarizing advances in knowledge on how to diagnose and treat these conditions,” Khan says. “Key recommendations from the upcoming global guidelines will also be presented.”

Bagley is the senior editor of Endocrine News. He wrote about the osteoporosis risk factors in men with higher BMIs in the June issue. 

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