(PO-114) (PO-114) Neuropsychiatric Hyperparathyroidism: Severe Psychosis Resolves With Parathyroidectomy

Background:

Dysregulation of calcium homeostasis in Primary Hyperparathyroidism (HPT) leads to a broad spectrum of neuropsychiatric symptoms, rarely psychosis. Despite the observed psychiatric manifestations of HPT these phenomena are poorly understood and can be under-appreciated contributors to psychiatric illness.



Case:

A 35 year-old Caucasian woman presented to the emergency department with insidious onset of paranoid delusions, hyperthymia, severe insomnia, and agitation. She demonstrated delusions of thought control, bodily possession, and implantation of explosives in her abdomen. She was detained by police after threatening herself with a knife. Psychiatric history was significant for Generalized Anxiety Disorder. Medical history was unremarkable. Family history is remarkable for Brief Psychotic Disorder. Workup revealed mild hypercalcemia, elevated parathyroid hormone, hypophosphatemia, with a 0.8cm hypoechoic lesion on thyroid ultrasound. The patient required constant IV hydration to maintain normal serum Ca⁺⁺, tolerated quetiapine 150mg nightly with residual psychiatric symptoms (hyperthymia, odd affect, staring, auditory hallucinations, retrograde amnesia) while awaiting definitive treatment. Endocrinology opined that mild hypercalcemia did not explain observed psychiatric symptoms and proposed outpatient surgical treatment. Considering the high acuity presentation and risk of decompensation Psychiatry advocated for emergent surgical intervention. After subtotal parathyroidectomy and adenoma excision she achieved rapid resolution of the principal neuropsychiatric features described above, quetiapine was discontinue in favor for aripiprazole 10mg prior to discharge.



Discussion:

Neuropsychiatric symptoms are a diverse feature of HPT yet little is known about their pathophysiology. Evidence suggests that cognitive and emotional dysfunction may be present in “asymptomatic” HPT (Agrawal, 2014). Ca⁺⁺ plays a pivotal role in critical cell processes including cellular apoptosis and neurotransmitter release, while PTH can independently incite calcium influx causing dysregulation in neurotransmission and hippocampal degradation (Hirasawa, 2000). Intracellular calcium overload can directly insult mitochondria, resulting in membrane instability and disruption of ATP synthesis (Orrenius, 2003). These in turn lead to widespread derangements in cellular metabolism and homeostasis which can cause or exacerbate psychotic illness. In this case the patient achieved partial remission with resolution of hypercalcemia and extraordinary improvement after surgical correction of HPT.



Conclusions:

Providers are cautioned not to use the degree of hypercalcemia as a prima facie method to rule out neuropsychiatric complications associated with HPT. Indeed psychosis is a severe manifestation of HPT which may warrant immediate surgical intervention.



References:

Orrenius S, Zhivotovsky B, Nicotera P: Regulation of cell death: the calcium-apoptosis link. Nature Reviews Molecular Cellular Biology July 2003; Volume 4, 552-565



Hirasawa T, et al.: Adverse effects of an active fragment of parathyroid hormone on rat hippocampal organotypic cultures. British Journal of Pharmacology 2000; 129, 21-28



Agrawal L, Habib Z, Emanuele N: Neurologic disorders of mineral metabolism and parathyroid disease. Handbook of Clinical Neurology, Vol. 120 2014; 737-748