Psychosomatics 48:265-268, June 2007
doi: 10.1176/appi.psy.48.3.265
© 2007 Academy of Psychosomatic Medicine
Mania in a Case of Hyperparathyroidism
Scott W. Brown, M.S.,
Barin V. Vyas, M.D., and
David R. Spiegel, M.D.
Received January 5, 2006; revised July 25, 2006; accepted August 8, 2006. From Eastern Virginia Medical School, Dept. of Psychiatry and Behavioral Sciences, Norfolk, VA. Send correspondence and reprint requests to David R. Spiegel, M.D., Eastern Virginia Medical School, Dept. of Psychiatry and Behavioral Sciences, 825 Fairfax Ave., Norfolk, VA 23507. e-mail: spiegedr{at}evms.edu
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ABSTRACT
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Psychiatric manifestations of primary hyperparathyroidism are mediated by hypercalcemia. To date, most evidence indicates that hypercalcemia and increased cerebrospinal-fluid calcium levels produce depression symptoms. Presented here is a case report of a 52-year-old woman in a manic state. She had no psychiatric history but had substantially elevated parathyroid hormone levels and hypercalcemia. On the basis of emerging evidence that calcium channel-blockers effectively treat mania, the authors propose that elevated calcium levels may act through multiple mechanisms or on various regions of the brain to produce a spectrum of psychiatric symptoms that should now include mania as a possibility.
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INTRODUCTION
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Mania, as described by DSM-IV-TR, is a condition exemplified by an unusually and persistently elevated expansive or irritable mood. Other symptoms encountered include grandiosity, decreased need for sleep, pressured speech, flight of ideas, tangentiality, distractibility, increase in goal-directed activities, psychomotor agitation, and engaging in activities with painful consequences. These symptoms, although typically associated with bipolar I disorder, may be seen in connection with DSM Mood Disorders Due to General Medical Conditions, Substance-Induced Mood Disorder, or Attention-Deficit/Hyperactivity Disorder. Hypomania is distinguished from mania in that there is not a marked impairment in social or occupational functioning, nor are there any psychotic symptoms.1
Hyperparathyroidism is a condition in which the parathyroid gland secretes high levels of parathyroid hormone. This hormone, in turn, increases serum calcium by increasing bone resorption, increasing intestinal absorption, and decreasing renal excretion. In primary hyperthyroidism, the parathyroid gland loses the ability to regulate parathyroid hormone secretion via a negative feedback mechanism with serum calcium levels.2 It has long been known to be a general-medical condition associated with psychiatric manifestations presenting as depression, catatonia, confusion, disorientation, fatigue, lethargy, emotional lability, or, occasionally, paranoid delusions and hallucinations.3–5 These effects are believed to be mediated through the increased calcium levels seen in hyperparathyroid states.6
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Case Report
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"Ms. W" is a 52-year-old African American woman whom the Consult–Liaison Service at Eastern Virginia Medical School was asked to evaluate to determine whether she had the capacity to make decisions related to her medical care and to leave the hospital against medical advice. Minimal history regarding her mental state was given at the time of the consultation.
Ms. W presented at admission with abdominal pain, nausea, and malaise. She had also experienced an unintentional loss of approximately 100 pounds over the past year. Her previous weight was 215 pounds. These symptoms closely resembled those she had had before another admission 5 months ago in which she was found to have an iron-deficiency anemia secondary to a benign antral gastric ulcer. She was transfused 2 units of blood in order to stabilize her hemoglobin and hematocrit. She was scheduled to be followed up as an outpatient for further work-up for the ulcer, as well as for hyperparathyroidism and hypertension discovered during the admission.
Before the current admission, Ms. W had not received any follow-up care. At presentation to the hospital, she commented that her abdominal pain had worsened over the past week. Previously, it would only act up after eating fatty or spicy foods and remain bad for 2 to 3 days. She also complained of increasing nausea during the week and occasional episodes of vomiting. She denied any melena or hematochezia.
Initial management during this admission required 4 units of transfused blood. During the course of her hospital stay, Ms. W’s hypertension and hypercalcemia were controlled; her ulcer, having been diagnosed H. pylori-positive, was being treated, and a work-up for hyperparathyroidism was completed. A sestamibi parathyroid scan revealed a possible parathyroid adenoma, and a computerized tomographic (CT) scan of her abdomen revealed an adrenal mass consistent with an adenoma. Given these concurrent findings, the medical teams were concerned about a possible diagnosis of multiple endocrine neoplasm. It was around this time that the patient became insistent that she be discharged, and the Psychiatry Dept. was consulted.
We found Ms. W in her room, dressed in a hospital gown, packing and unpacking her belongings away in a shopping bag. She appeared quite agitated, but was agreeable to speaking with us. However, the exam abruptly ended after the patient realized we were from the Psychiatry Dept. Our exam revealed a patient with rapidly pressured speech that was difficult to interrupt. Her thought process bordered on tangential, with loose associations. Her mood was irritable. She appeared hypersexual, as evidenced by the content of her speech and actions. She had a very short attention span and was highly distractible. Her plan to leave the hospital could have represented "involvement in activities with painful consequences." We attempted to ascertain any decreased need for sleep before the admission, but Ms. W did not answer the questions because of her tangentiality symptoms.
According to collateral histories taken, the patient exhibited paranoid psychosis in the form of believing someone was trying to have sex with her husband when she went to visit him on a previous night. Her husband was concurrently in the hospital after a stroke, so that the accusation had no merit. She was also described as tearful and upset throughout an interview done the day before Psychiatry had seen her. She denied any auditory or visual hallucinations, as well as any inclination to harm herself or others. We could not do a formal mental status exam because of the patient’s inability to attend.
Ms. W’s previous medical history includes peptic ulcer disease, hypertension, hypercalcemia, hyperparathyroidism, a gunshot wound to the abdomen, and a ventral hernia. She has no known medical allergies. She takes no medicines when not in the hospital. She was discharged from the hospital 5 months ago on metoprolol 50 mg bid, lisinopril 20 mg qd, pantoprazole 40 mg bid, and senna and docusate sodium, 1–2 tablets qhs as needed for constipation. There is no indication that she was compliant with this drug regimen. During this admission, treatment for her iron-deficiency anemia required four transfusions acutely and ferrous sulfate 325 mg tid to correct the underlying iron deficiency. Her hypertension was initially managed with furosemide 20 mg tid, but this was changed to amlodipine 5 mg qd before the end of her hospital stay. She received one treatment of pamidronate 60 mg to treat any hypercalcemia caused by bone demineralization. The H. pylori-positive ulcer was treated with metronidazole 250 mg tid, pantoprazole 40 mg bid, Pepto-Bismol, and tetracycline 500 mg tid.
On multiple collateral histories, the patient denied any psychiatric history in herself or her family members. She noted that she had quit drinking alcohol 3 years earlier, but it is unknown how much she drank before that time. She smokes one-half pack of cigarettes per day. At the time of her previous admission, her urine drug screen was negative, and she had no alcohol in her blood. She lives at home with her husband, who has suffered several strokes. She is his primary caregiver.
Ms. W had a critical hemoglobin of 5.2 g/dl and a hematocrit of 16.7% on the first day of this admission; these rose to 10.2 g/dl and 31.2%, respectively, by the last day of her hospitalization. She never demonstrated any signs of infection, with a stable white blood count, normal urinalysis, normal temperature, and no growth on blood cultures. The two lab values most notable at admission were an elevated serum calcium of 14.8 mg/dl and an intact parathyroid hormone of 676.2 pg/ml. She was followed during the hospitalization, with ionized calcium levels beginning at 6.9 mg/dl, falling to a slightly low value of 4.0 mg/dl on the final day. In working up various etiologies of hypercalcemia, vitamin D1,25 and 25-OH Vitamin D were determined to be normal, and a 24-hour urine calcium level was also normal. Her magnesium and phosphorous levels remained low during the course of treatment, ranging from 1.1 mg/dl to 1.7 mg/dl magnesium and 1.1 mg/dl to 1.8 mg/dl phosphorous. Her lipase was slightly elevated upon admission, at 83 U/liter, and she had normal levels of AST, ALT, alkaline phosphatase, and total and direct bilirubin. Gastrin levels ranged from a normal 81 pg/ml to an elevated 234 pg/ml. A 24-hr. urine sample collected on the final day of the patient’s admission demonstrated 1.7 mg/24 hrs. vanillylmandelic acid (VMA), 41 µg/24 hrs. metanephrine, and 109 µg/24 hrs. normetanephrine, which were all normal, but results were not reported until after the patient had left the hospital.
The Psychiatry Consult Service determined that Ms. W did not have an appreciation of the gravity of her medical condition and that her decision-making ability was severely impaired by her manic/hypomanic symptoms. Therefore, it was the judgment of our team that she did not have the capacity to make medical decisions. Our working differential diagnosis was mania due to her general-medical condition of hyperparathyroidism, or bipolar affective disorder, although there was no history to indicate this to be the case. We recommended beginning the patient on aripiprazole 5 mg bid and olanzapine 5 mg every 8 hrs. as needed for agitation. Her primary medical team was working on obtaining a temporary medical detaining-order, because of their concern over the possibility of her having a pheochromocytoma, when she left the hospital against medical advice. There has been no follow-up since that time.
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Discussion
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This case demonstrates a clinical picture of mania in a patient suffering from the effects of hyperparathyroidism. Traditionally, depression has been the psychiatric symptom associated with hypercalcemia, although the use of calcium channel-blockers to treat mania suggests that hypercalcemia may trigger manic episodes.7–10 Calcium influx at the presynaptic nerve terminal induces the release of neurotransmitters into the synaptic cleft.11
It can be inferred from this that if the extraneuronal environment has a higher concentration of calcium, the influx triggered by nerve membrane depolarization would be increased, resulting in a greater magnitude of neurotransmitter release. Interestingly, one proposed mechanism by which lithium, the first-line treatment for bipolar mania, acts, is to increase the availability of inositol 1,4-triphosphate and thereby increase cytosolic calcium levels.12
The fact that both of these medications are utilized in the treatment of mania, a possible causal role of calcium in the etiology of mood disorders cannot be dismissed, despite its probable multifactorial pathogenesis.
Also, multiple brain studies have been conducted showing evidence suggesting that bipolar patients have subcortical influence in the right head of the caudate and right thalamus, while unipolar manic patients have a greater right-cortical orbitofrontal and basotemporal contribution.13–15 These two dichotomous mechanisms by which the symptoms of mania may be controlled and the various organic sources for the disease imply that although tradition dictates that hypercalcemia associated with hyperparathyroidism often presents with depressive symptoms, a manic picture is not beyond consideration.
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REFERENCES
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- American Psychiatric Association: Mood Disorders, in Diagnostic and Statistical Manual of Mental Disorders: DSM-IV-TR, 4th Ed. Washington, DC, American Psychiatric Publishing, Inc., 2000, pp 345-428
- Geffken GR, Ward HE, Staab JP, et al: Psychiatric morbidity in endocrine disorders. Psychiatr Clin North Am 1998; 21:473–489[CrossRef][Medline]
- Gatewood JW, Organ CH Jr, Mead BT: Mental changes associated with hyperparathyroidism. Am J Psychiatry 1975; 132:129–132[Abstract/Free Full Text]
- Alarcon RD, Franceschini JA: Hyperparathyroidism and paranoid psychosis. case report and review of the literature. Br J Psychiatry 1984; 145:477–486[Abstract/Free Full Text]
- Spivak B, Radvan M, Ohring R, et al: Primary hyperparathyroidism, psychiatric manifestations, diagnosis and management. Psychother Psychosom 1989; 51:38–44[CrossRef][Medline]
- Jimerson DC, Post RM, Carman JS, et al: CSF calcium: clinical correlates in affective illness and schizophrenia. Biol Psychiatry 1979; 14:37–51[Medline]
- Hollister LE, Trevino ES: Calcium channel blockers in psychiatric disorders: a review of the literature. Can J Psychiatry 1999; 44:658–664[Medline]
- Dubovsky SL, Franks RD, Allen S, et al: Calcium antagonists in mania: a double-blind study of verapamil. Psychiatry Res 1986; 18:309–320[CrossRef][Medline]
- Dubovsky SL, Franks RD, Lifschitz M, et al: Effectiveness of verapamil in the treatment of a manic patient. Am J Psychiatry 1982; 139:502–504[Free Full Text]
- Keller S, Frishman WH: Neuropsychiatric effects of cardiovascular drug therapy. Cardiol Rev 2003; 11:73–93[CrossRef][Medline]
- Stanley EF: The calcium channel and the organization of the presynaptic transmitter-release face. Trends Neurosci 1997; 20:404–409[CrossRef][Medline]
- Ulrich ML, Rotzinger S, Asghar SJ, et al: Effects of dextroamphetamine, lithium chloride, sodium valproate, and carbamazepine on intraplatelet Ca2+ levels. Psychiatry Neurosci 2003; 28:115–125
- Blumberg HP, Stern E, Ricketts S, et al: Rostral and orbital prefrontal cortex dysfunction in the manic state of bipolar disorder. Am J Psychiatry 1999; 156:1986–1988[Abstract/Free Full Text]
- Jorge RE, Robinson RG, Starkstein SE, et al: Secondary mania following traumatic brain injury. Am J Psychiatry 1993; 150:916–921[Abstract/Free Full Text]
- Starkstein SE, Fedoroff P, Berthier ML, et al: Manic-depressive and pure manic states after brain lesions. Biol Psychiatry 1991; 29:149–158[Medline]
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ABSTRACT
INTRODUCTION
