Association Between Primary Hyperparathyroidism and Secondary Diabetes Mellitus: Findings From a Scoping Review

Abstract

An ill-defined association exists between diabetes mellitus (insulin resistance) and primary hyperparathyroidism. This article explores this phenomenon while providing an explanation for such a relationship and reviewing the evidence regarding the response to insulin sensitivity following a parathyroidectomy. Primary hyperparathyroidism may increase the risk of developing insulin resistance; peculiarly, this is not present in all patients. It is likely that both intracellular hypercalcemia and hypophosphatemia alter the insulin receptor expression and response; the contribution of parathyroid hormone is less clear. Following parathyroidectomy, patients may demonstrate improvement in their insulin sensitivity, while others have no response or a detrimental effect. A varied phenotype exists among patients, and furthermore, it is unclear why certain patients demonstrate improvement in insulin sensitivity following a parathyroidectomy, whereas others fail to do so. While this review provides a broad overview of the general endocrine community, it is imperative to note that clinical applicability is limited until further studies address these remaining uncertainties. Due to the lack of understanding regarding this endocrinological enigma, the presence of insulin resistance, at this present time, should not be a criterion for a parathyroidectomy.

Primary Hyperparathyroidism and Cardiovascular Disease: An Association Study Using Clinical Natural Language Processing Systems and Big Data Analytics

“…There is some evidence of an association between PHPT and type 2 diabetes mellitus (T2DM), but the exact nature of their relationship is not fully understood and more research is needed to better understand the underlying mechanisms. Some studies have found that people with PHPT may have an increased risk of developing insulin resistance and, therefore, an increased risk of developing T2DM [39]. However, other studies in patients with normocalcemic PHPT have failed to demonstrate an association with insulin resistance [40].…”

Turning Points in Cross-Disciplinary Perspective of Primary Hyperparathyroidism and Pancreas Involvements: Hypercalcemia-Induced Pancreatitis, MEN1 Gene-Related Tumors, and Insulin Resistance

“…The presence of insulin resistance stands for an additional turning point between the parathyroid field and pancreas involvement. Whether this specific instance is incidental or calcium- and PTH-related anomalies act as contributors to pancreas-related insulin secretion and peripheral resistance at its receptors is still an open issue [ 146 , 147 ].…”

“…There is evidence that high levels of calcium and low serum phosphorus (the biological aspects in primary hyperparathyroidism) alter the modulation of the insulin receptor, whereas excessive PTH concentration does not directly influence the insulin signal transduction pathway [ 146 ]. However, studies on patients without the diagnosis of primary hyperparathyroidism (such as NHANES cohort) showed that high serum PTH is positively correlated with the severity of metabolic syndrome if PTH is elevated at baseline [ 148 ].…”

“…Notably, not all patients displayed these post-operatory cardio-metabolic dynamics, while at baseline, only a distinct subgroup of subjects had a higher prevalence of metabolic issues. Currently, the presence of metabolic syndrome in primary hyperparathyroidism does not represent an indication itself for parathyroidectomy according to guidelines [ 146 ].…”

Vitamin D, Parathyroid Hormone, Insulin Sensitivity and Islet <i>β</i>-Cell Secretory Function in Diabetic Patients from South Kivu in the Democratic Republic of Congo: Cross-Sectional Study

“…Thus, a high prevalence of low vitamin D level drives an equally high prevalence of secondary hyperparathyroidism. Hyperparathyroidism also contributes to insulin resistance, promoting incident T2DM by pathophysiological mechanisms complementary to those of low vitamin D level [7] [8].…”