Cognitive deficits in primary hyperparathyroidism – what we know and what we do not know: A narrative review

Classic symptoms of primary hyperparathyroidism (PHPT) are seen in approximately 20% of patients. While features such as kidney stones and skeletal disease are often highlighted as directly related to the disease, others can be even more prevalent. For example, cognitive dysfunction and reduced quality of life are common complaints in many patients, even among those who are classified as being asymptomatic. The pathophysiology of PHPT involves the impact of excess parathyroid hormone (PTH) on calcium metabolism. Referencing putative neurocognitive issues, many animal studies have illustrated the potential roles of PTH and PTH receptors in the brain. Functional imaging and pre-and post-parathyroidectomy studies have suggested a link between the neuronal impact of elevated PTH levels on specific functional aspects of the central nervous system, such as cognition. Confounding a direct role for PTH are hypercalcemia and vitamin D deficiency, both of which could conceivably alter CNS function in PHPT. The lack of strong evidence that parathyroidectomy improves cognition in patients with PHPT raises the question as to whether parathyroid surgery should be recommended on this basis alone. This narrative review summarizes the available literature on neurocognitive function in PHPT.