A Clinical Review of the Psychiatric Sequelae of Primary Hyperparathyroidism

Abstract

Despite one-quarter of patients with primary hyperparathyroidism (PHPT) experiencing psychiatric symptoms, there remains a dearth of literature regarding the diagnosis and further management of psychiatric sequelae in PHPT. We aim to review the literature pertaining to the epidemiology, disease presentation, pathophysiology, diagnostics, and therapeutics regarding psychiatric sequelae of PHPT with an emphasis on clinical pearls for practicing psychiatrists. A literature search was conducted using the US National Library of Medicine's PubMed resource using the following keywords in various combinations: primary hyperparathyroidism, neuropsychiatric, calcium, psychosis, mania, depression, catatonia, delirium, parathyroidectomy, and psychotropic medication. We discuss in depth all aspects of the diagnosis and management of psychiatric sequela in PHPT. We have also identified epidemiological trends, discussed the most common clinical presentations, and postulated possible mechanisms for psychiatric symptoms in PHPT. Psychiatrists should maintain diagnostic suspicion for PHPT in older adult female patients presenting with new-onset psychiatric illness. Several mechanisms involving the following may explain the variety of psychiatric symptoms in PHPT: tyrosine hydroxylase, parathyroid hormone, interleukin-6, monoamine oxidase, calcium, and the sodium-potassium adenosine triphosphatase transporter. We recommend psychiatrists take a symptom-oriented approach to management. Treating a patient's psychosis, mania, depression, catatonia, delirium, or eating disorder pathology via conventional therapeutics seems like a rational approach despite the underlying medical etiology. Only parathyroidectomy has been proven to be definitive in the complete amelioration of psychiatric symptoms.

Keywords: adult primary hyperparathyroidism; behavioral endocrinology; clinical neuroscience; consultation liaison psychiatry; psychosomatic psychiatry.

Figure 1. Consort diagram depicting our identification of papers focusing on psychiatric aspects of primary hyperparathyroidism

Figure 2. Proposed pathophysiologic correlates of psychiatric symptomatology in primary hyperparathyroidism

BBB = blood brain barrier, PTH = parathyroid hormone, IL-6 = interleukin-6, Na/K-ATPase = sodium-potassium adenosine triphosphatase transporter, MAO = monoamine oxidase, PTH2R = PTH2 receptors, ??? = unknown mechanisms

Figure 3. General diagnostic schema for hypercalcemia

Of note, this does not account for clinical scenarios where ionized calcium measurements may be indicated, for cases of early disease, or normocalcemic variants of primary hyperparathyroidism. PHPT = primary hyperparathyroidism, PTH = parathyroid hormone, FHH = familial hypocalciuric hypercalcemia