European experts in endocrinology met recently to discuss the unmet scientific and educational needs in parathyroid diseases.
European experts in endocrinology met recently to discuss the unmet scientific and educational needs in parathyroid diseases, especially parathyroid cancer (PC), as well as primary hyperparathyroidism (PHPT) and hypoparathyroidism (HypoPT).
The European Society of Endocrinology (ESE) created a program (called PARAT) to focus on these issues. At a workshop last year in the Netherlands, they noted that benign parathyroid adenomas and hyperplasia is common in office settings, but PC is rare, and little is known about its pathogenesis.
PHPT is prevalent in Western countries, yet evidence is also lacking about its natural history and whether morbidity and long-term outcomes are related to hypercalcemia, plasma parathyroid hormone (PTH) concentrations, or both. Treating PHPT has not yet been shown to reverse the risk of cardiovascular deaths or fractures. PHPT is very common, especially in postmenopausal women.
PC accounts for fewer than 1% of PHPT cases, but it is increasing. The researchers wrote that international studies are needed to understand the genetic mechanisms, biomarkers for disease activity, and optimal treatments.
About 20% of PCs demonstrate high mutational burden, and identifying targetable DNA variations, gene amplifications and gene fusions may facilitate personalized treatment, such as immunotherapy or targeted therapy.
Due to the rarity of PC, the workshop participants said no cancer center can claim a high level of experience, and central registries of patients are needed. A multinational registry could allow for second opinions at the histopathological level, and for long-term follow-up of patients.
In addition, there is a need for rigorous diagnosing of chronic HypoPT, a designated orphan disease that is associated with a high risk of complications. The workshop participants suggest using the ESE definition of low calcium levels with low or inappropriate low levels of PTH.
HypoPT impairs a patient’s quality of life, including a fluctuation or decline of cognitive skills. Most cases of HypoPT are discovered secondary to neck surgery. There is a need for a better understanding of the role of in situ parathyroid gland preservation in the prevention of HypoPT following surgery and to gain knowledge on the potential parathyroid reserve.
The relationship between biomarkers of the disease (calcium levels) and intellectual function need to be better understood, as well as the role of PTH.
PC should be suspected in patients with severe PTH-dependent hypercalcemia or its complications, but it may be overlooked because it is so rare, the researchers wrote.
Bollerslev J, Schalin-Jäntti C, Rejnmark L, et al. Unmet therapeutic, educational and scientific needs in parathyroid disorders: Consensus statement from the first European Society of Endocrinology Workshop (PARAT) [published online June 7, 2019]. doi: 10.1530/EJE-19-0316.