Neuropsychiatric manifestations of primary hyperparathyroidism

Neuropsychiatric manifestations occur in about 25% of patients with primary hyperparathyroidism (PHPT). Symptoms can range from depression, anxiety, fatigue or cognitive dysfunction which are commonly observed to more seldomly revealed states of mania, delirium or psychosis which warrant psychiatric intervention. The underlying pathophysiology is likely multifactorial, potentially explained by elevated parathormone and hypercalcemia, with subsequent direct and indirect effects on monoamine neurotransmission and neuroinflammation via monoamine oxidase, tyrosine hydroxylase, sodium-potassium adenosine triphosphatase transporter and interleukin‑6.This review aims to (1) give an overview of the hypothesized pathophysiologic understanding regarding neuropsychiatric manifestations, (2) to summarize the most common neuropsychiatric symptoms and (3) to equip clinicians with recommendations for evidence-based tools to detect neuropsychiatric symptoms effectively.Psychometric questionnaires depicting psychiatric symptom burden across PHPT research are highlighted. Cut-off values for psychiatric screening purposes and hypothesized cut-off values in PHPT research to indicate parathyroidectomy are provided. A practical approach on how screening for neuropsychiatric symptoms in PHPT might be implemented in routine clinical practice is outlined.Parathyroidectomy is recognized to alleviate neuropsychiatric symptoms in PHPT, with increasing evidence showing persistent improvements in symptoms of depression, anxiety, fatigue and cognitive dysfunction. Clinical practice guidelines still diverge on whether neuropsychiatric manifestations in PHPT warrant parathyroid surgery. A symptom-based treatment approach is recommended alongside evaluating surgical intervention.