Unmet therapeutic, educational and scientific needs in parathyroid disorders: Consensus Statement from the first European Society of Endocrinology Workshop (PARAT)

Abstract

PARAT, a new European Society of Endocrinology program, aims to identify unmet scientific and educational needs of parathyroid disorders, such as primary hyperparathyroidism (PHPT), including parathyroid cancer (PC), and hypoparathyroidism (HypoPT). The discussions and consensus statements from the first PARAT workshop (September 2018) are reviewed. PHPT has a high prevalence in Western communities, yet evidence is sparse concerning the natural history and whether morbidity and long-term outcomes are related to hypercalcemia or plasma PTH concentrations or both. Cardiovascular mortality and prevalence of low energy fractures are increased, whereas quality of life is decreased, although their reversibility by treatment of PHPT has not been convincingly demonstrated. PC is a rare cause of PHPT, with increasing incidence, and international collaborative studies are required to advance knowledge of the genetic mechanisms, biomarkers for disease activity and optimal treatments. For example, ~20% of PCs demonstrate high mutational burden, and identifying targetable DNA variations, gene amplifications and gene fusions may facilitate personalized care, such as different forms of immunotherapy or targeted therapy. HypoPT, a designated orphan disease, is associated with a high risk of symptoms and complications. Most cases are secondary to neck surgery. However, there is a need to better understand the relation between disease biomarkers and intellectual function and to establish the role of PTH in target tissues, as these may facilitate the appropriate use of PTH substitution therapy. Management of parathyroid disorders is challenging, and PARAT has highlighted the need for international transdisciplinary scientific and educational studies in advancing in this field.

Epidemiology and management of parathyroid gland disorders in Spain over 15 years: A retrospective multicentre analysis

“…In parallel, international Workshop guidelines were updated in 2014 with recommendations to evaluate renal and skeletal involvement prior to parathyroid surgery in patients with primary hyperPT, while maintain the recommended age under 50 years [24]. The most recent guidelines for the management and treatment of primary hyperPT have been published by the National Institute for Health and Care Excellence of England and the PARAT program focusing on parathyroid gland disorders established by The European Society of Endocrinology [3,25]. Similarly, recommendations have been established for secondary and tertiary hyperPT and hypoPT [10,17].…”

Hypoparathyroidism, deafness, and renal dysplasia syndrome: 20 Years after the identification of the firstGATA3mutations

“…ing is necessary as overtreatment may result in hypercalciuria and nephrocalcinosis, which is of particular concern in HDR patients with underlying renal defects (Gafni & Collins, 2019). Recombinant PTH replacement therapy can be considered in patients with chronic hypoparathyroidism, who cannot be adequately controlled with standard therapy alone (Bollerslev et al, 2019;Mannstadt et al, 2017), but so far, there have been no reports of patients with HDR treated in this way. Early diagnosis and correction of hearing impairment, which is often present from birth, is essential to prevent any impact on language and future education.…”

Osseous Manifestations of Primary Hyperparathyroidism: Imaging Findings

“…Primary hyperparathyroidism (PHPT) is a main disease subtype with classical and normocalcemic variants. Hypercalcemia is evident in patients with classical PHPT, while the normocalcemic variant demonstrates normal total and ionized calcium levels after correcting for albumin [2][3][4]. Classical PHPT is most commonly asymptomatic and due to autonomous secretion of parathyroid hormone from a benign parathyroid adenoma in 80% of patients with lack of feedback inhibition of calcium [1,4,5].…”

“…Metabolic bone disease is an established clinical manifestation of PHPT as PTH is a major regulator of osteoclast activity and bone remodeling [8]. In addition, the biomechanical properties of bone as seen in PHPT's variants, including fracture risk and protective bone treatment, are an area of ongoing scientific interest [3]. However, the clinical and physical symptoms as well as imaging findings that have been historically taught are considered relatively rare today in clinical presentation and context.…”