Should ‘Mild Primary Hyperparathyroidism’ be reclassified as ‘insidious’: is it time to reconsider?

Abstract

Summary Primary hyperparathyroidism (PHPT) is a common incidental finding on routine biochemical testing, affecting around 1% of the population. The majority of individuals will be asymptomatic at diagnosis, with no evidence of end organ damage, and unless individuals aged <50 years at diagnosis, they are often considered to have ‘mild’ PHPT, as they do not meet published criteria for parathyroidectomy (PTX). However, there is increasing evidence that ‘mild’ PHPT is associated with adverse health outcomes. Long‐term observational studies describing the natural history of ‘mild’ PHPT suggest that even though biochemistry may be relatively stable in the majority, bone mineral density (BMD) does decline after approximately 10 years of observation, whereas significant improvements in BMD are seen following PTX. Recent large European record linkage studies of ‘mild PHPT’ demonstrate significantly increased all‐cause and cardiovascular mortality, similar to rates published for patients with PHPT who meet the NIH surgical criteria. ‘Mild’ PHPT was also associated with increased admissions for nonfatal cardiovascular disease, renal failure, renal stones, fractures, hypertension, psychiatric disease, cancer and diabetes, suggesting that ‘insidious’ PHPT may be a more appropriate description, or at least that the term ‘mild’ should be abandoned. Randomized controlled trials (RCTs) have begun to explore the benefits of PTX in this condition, demonstrating improvements in BMD and some psychiatric outcomes at approximately 2 years of follow‐up. However, larger, adequately powered, long‐term, RCTs will be required to determine whether PTX improves potential long‐term morbidity and mortality in patients with PHPT who do not meet standard surgical criteria.

Cardiovascular risk and metabolic syndrome in primary hyperparathyroidism and their correlation to different clinical forms

“…Consistently, also normocalcemic PHPT has been associated to metabolic and cardiovascular abnormalities [26,27]. These data are in line with recent consideration of MacFarlane et al [28] who suggest that "mild PHPT," that commonly refers to individuals not meeting the NIH criteria for parathyroidectomy, should be reclassified as an insidious disease. Therefore, our results indicate that low-risk asymptomatic patients should be assessed and properly treated also by parathyroidectomy, just like symptomatic and high-risk asymptomatic PHPT.…”

What predicts adverse outcomes in untreated primary hyperparathyroidism? The Parathyroid Epidemiology and Audit Research Study (PEARS)

“…It appears that elevated PTH concentrations may have a direct adverse effect on CV health. This is plausible, as in vitro PTH does have effects on vascular smooth muscle and endothelium‐dependent vasodilation in addition to inotropic and chronotropic effects on cardiac myocytes …”

Interdisciplinary Aspects of Primary Hyperparathyroidism: Symptomatology in a Series of 100 Cases

“…In the current study, 58% of the patients with PHPT suffered from at least one of the following CVDs: ischemic heart disease (IHD), HA or stroke, just as reported in other studies [17,[39][40][41]. It has been suggested that the severity of PHPT may determine the presence of cardiovascular manifestations [42].…”

“…This question definitely needs more investigation. Especially, in light of the fact that PHPT has been associated with an increased risk of mortality, particularly from cardiovascular diseases (CVD) [17,[39][40][41].…”