New Hypoparathyroidism Guidelines and Emerging PTH Replacement Therapies for Improved Patient Outcomes

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New guidelines from the Second International Workshop on the Evaluation and Management of Hypoparathyroidism provide clinicians with the latest evidence-based recommendations for the prevention, diagnosis and management of this rare disease.

“These guidelines offer practical advice for clinical endocrinologists in the community who want to be sure they’re practicing at the standard of care,” said UCSF endocrinologist Dolores Shoback, MD, who participated in the Workshop and co-wrote the guidelines. The Workshop was completed during the pandemic, with experts worldwide collaborating to achieve consensus.

In hypoparathyroidism, the parathyroid glands don’t produce enough parathyroid hormone (PTH) or the produced PTH lacks biologic activity, resulting in abnormally low calcium and elevated phosphorus levels in the blood. This can lead to symptoms and complications affecting the renal, skeletal, neuromuscular and cardiovascular systems. Patients with the condition are also at risk for cataracts.

Managing a high burden of disease

“This is a rare, chronic disease. Day-to-day symptoms can be significant and interfere with quality of life for patients,” Shoback said. “They have the propensity to develop kidney stones and chronic kidney disease. Their bones can be abnormally dense. They need frequent blood tests, checks of kidney function and calcium levels, and ophthalmology evaluations for cataracts. A lot of these patients have a high burden of disease because they may have other conditions, like heart disease or high blood pressure. Hypoparathyroidism can affect how those other conditions behave and are treated.”

The new guidelines cover:

Diagnosis
Minimizing the risks of chronic postsurgical hypoparathyroidism to different organ systems
Predicting permanent postsurgical hypoparathyroidism by measuring PTH
Genetic testing
Symptoms and complications
Optimal monitoring strategy
Managing patients with hypoparathyroidism – first-line treatments and PTH therapy
Management recommendations during pregnancy and lactation

“The process for formulating the guidelines took two years,” Shoback said. “We looked at all the existing evidence and tried to give clinicians the best recommendations for diagnosis and management.

“About 75% of adult cases of hypoparathyroidism are due to postsurgical complications,” she continued. “There was a lot of participation in the Workshop by the surgical community, and we came to an agreement on the definition of the disease. That was a great collaboration.” Panel members defined hypoparathyroidism as permanent when it persists more than 12 months after surgery. The guidelines include recommendations for minimizing the risk of permanent postsurgical hypoparathyroidism.

“We determined when to measure PTH and calcium after a thyroidectomy and what action to take based on the levels,” Shoback said. The guidelines recommend using PTH measurements 12 to 24 hours after total thyroidectomy. If PTH values are greater than 10 pg/mL, the patient is unlikely to develop permanent hypoparathyroidism, therefore long-term treatment with active vitamin D and calcium supplements isn’t needed. “This is an important branch point in the immediate hours after thyroid surgery.”

Guidance for genetic testing and managing hypoparathyroidism in patients who are pregnant or nursing is also provided.

PTH therapy clinical trial

Conventional treatment for hypoparathyroidism includes oral calcium and active vitamin D. For patients whose disease isn’t well controlled by these first-line treatments, PTH therapy is a promising option but not yet the standard of care.

UCSF is involved in the PaTHway clinical trial, a phase 3 study of TransCon PTH, an investigational PTH replacement therapy administered subcutaneously once daily in adults with hypoparathyroidism. Published results from the trial, cowritten by Shoback, show that TransCon PTH improved and maintained patients’ serum calcium levels in the normal range, allowing independence from conventional therapy.

“The guidelines provide a framework for patients who aren’t well controlled on conventional management and who might be candidates for injectable PTH therapy,” Shoback said.

Investigating transplantation as an emerging treatment

UCSF researchers, including transplant surgeon Peter G. Stock, MD, and endocrine surgeon Julie Ann Sosa, MD, MA, FACS, chair of the UCSF Department of Surgery and president of the American Thyroid Association, are investigating parathyroid allotransplantation as a potential treatment for severe hypoparathyroidism. They published a 2022 study with promising results on the viability and functional integrity of donor parathyroid glands following procurement.

Expert multidisciplinary care at UCSF

In addition to Shoback, UCSF endocrinologists with expertise in hypoparathyroidism include Chienying Liu, MD, and Edward C. Hsiao, MD, PhD. Patients are evaluated and managed by a team of multidisciplinary specialists. According to Shoback, nonsurgical cases of hypoparathyroidism are often due to a genetic condition that can be defined by specialized testing. “UCSF has an excellent genetics department, and patients can consult with our genetic counselors,” she said.

According to a study led by Sosa, a surgeon volume threshold of more than 25 thyroidectomies a year is associated with the lowest risk of complications. At the UCSF Endocrine Surgery and Oncology Clinic, six high-volume endocrine surgeons each exceed that number of thyroid surgeries annually with excellent patient outcomes.

“We provide our patients with a high level of specialty care,” Shoback said.