Psychosomatics 40:486-490, December 1999
© 1999 The Academy of Psychosomatic Medine
Psychiatric Aspects of Parathyroid Disease
P. Joel Velasco , M.D.,
Manoochehr Manshadi, M.D. ,
Kevin Breen, M.D., and
Steven Lippmann, M.D.
Received February 3, 1999; revised April 7, 1999; accepted May 20, 1999. From Central State Hospital, Louisville, Kentucky; and the University of Louisville School of Medicine, Department of Psychiatry and Behavioral Science, Louisville, Kentucky. Address correspondence and reprint requests to Dr. Lippmann, University of Louisville Hospital, 5 East, 530 S. Jackson Street, Louisville, KY 40202.
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ABSTRACT
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Parathyroid diseases can present with psychiatric symptoms and can be recognized through determinations of serum electrolytes, especially the calcium level. Psychiatric evaluations should include a serum calcium concentration test, which is also essential in reassessment of patients poorly responsive to mental illness treatment. A magnesium and a phosphate assay may also be diagnostically helpful. Abnormality of divalent cation levels may provide evidence for consideration of, or ruling out, parathyroid disorders. Determinations of parathyroid hormone are performed if clinically indicated, and if abnormal divalent cation quantifications are confirmed. If parathyroid disease is identified, corrective endocrine therapies may diminish or even cure psychiatric aspects of parathyroid pathology. Failure to recognize a parathyroid disorder leaves an endocrine-induced mental dysfunction without proper treatment.
Key Words: Calcium • Psychiatric Presentations • Parathyroid Hormone
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INTRODUCTION
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Endocrinopathies are well established as being in the differential diagnosis of patients with mental illnesses. Parathyroid disorders, including hyperparathyroidism and hypoparathyroidism, are associated with psychiatric presentations that may preceed somatic manifestations as the initial findings. Abnormalities in the serum calcium assay are important early markers of when to consider parathyroid disease in a diagnostic workup. The common, routine, automated chemistry profile, which includes a calcium determination, is a simple screening method. It is critical that the calcium level be maintained as a screening test, despite certain cost-cutting measures in current practice.
Parathyroid hormone (PTH) determinations, serum testing for magnesium and phosphate concentrations, and scintigram scanning procedures of the parathyroid glands are other parts of the assessment. With a lack of uniformity in the laboratory testing methods for parathyroid hormone, reference standards vary accordingly. By using the most typical technique, a mid-molecule radioimmunoassay, the hormonal normal ranges are 29–85 pmol/L. PTH values acceptable for children and pregnant females are somewhat higher than that for other healthy adults. Figure 1, using the calcium and parathyroid hormone concentrations, may offer guidance for the differential diagnostic workup. Proper treatment of parathyroid pathology may potentially be curative of psychiatric symptoms.
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CALCIUM AND MAGNESIUM
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Hypercalcemia is common among patients with hyperparathyroidism; annual incidence is in the 0.1% range1 or up to 0.2% in adults over age 60.2 When hypercalcemia is detected, it is not only important to screen for hyperparathyroidism, but also to rule out other etiologies such as malignancy or drug-induced calcium elevation. Clinical presentations include gastrointestinal distress, peripheral neuromuscular complaints (e.g., weakness), nephrolithiasis, osteopenia, and psychiatric manifestations (e.g., lethargy, depression, delirium, psychosis, or anxiety). Similar clinical findings occur with hypermagnesemia. Cardiac observations include electrocardiographic shortening of QT intervals, rhythm disturbances, and even cardiac death.
Hypocalcemia, on the other hand, and hypomagnesemia both evidence a disturbing pattern of increased neuromuscular irritability and may occur in hypoparathyroidism. Other clinical features include muscle spasm, convulsions, and abdominal cramps. A prolongation of the QT interval or cardiac arrhythmias can also be seen. Depression, anxiety, psychosis, irritability, and intellectual impairment are prominent psychiatric findings.
Hypomagnesemia is documented in vomiting and malnutrition, including alcohol abuse and some prolonged intravenous feedings; it is also noted in hypoparathyroidism.3 Determinations of magnesium in blood are not routinely requested. Consider ordering a serum magnesium level in cases of abnormal calcium concentrations, postoperatively in parathyroid disorder patients, and in those persons with severe emesis or inadequate diet (e.g., as in alcoholism). Renal failure may result in elevated magnesium assays.
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HYPERPARATHYROIDISM
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Hyperparathyroidism is frequently associated with significant psychiatric symptoms. Delirium or dementia, depression, anxiety, psychosis, lethargy or apathy, and stupor or even coma can be observed in people with this endocrinopathy.4 Other than several isolated case reports over the past few decades, there are relatively few modern literature documentations about the epidemiology of psychopathology in hyperparathyroidism. A recent study in 18 subjects nonspecifically documented preoperative psychological distress, which was attenuated after surgical removal of parathyroid adenomata.5 Other reports reveal about half of the patients with hyperparathyroidism evidencing psychological complaints.6,7 Anxiety was a common finding, and severity was related to the degree of calcium elevation. One prospective series of 34 hyperparathyroid patients cited nearly one-third to be without psychiatric symptoms, one-third evidencing affective presentations, and 39% being cognitively impaired.8 The degree of serum calcium elevation correlated somewhat with psychopathology; affective complaints were more common in modest electrolyte elevations while encephalopathies were related more often to higher calcium concentrations.
Prominent mental and neuromuscular presentations characterize an analysis of 33 cases of primary hyperparathyroidism.9 Such manifestations dominated the picture in four of the subjects, with marked improvement occurring after parathyroid adenoma removal. Significant elevations of the serum calcium assay often characterize the initial finding in the laboratory results of hyperparathyroidism. Elevated parathyroid hormone concentrations are expected, and a low phosphate level is documented in some cases.
An incidence of psychopathology at 4% out of 405 cases is reported in a literature review of hyperparathyroidism.9 These presentations are divided into three main categories: 1) confusional state with clouding of consciousness, ranging from drowsiness to stupor; 2) clear sensorium with depression, psychosis (especially paranoid delusions), and violent or bizarre behavior; and 3) a "pseudoneurotic" form. This latter group evidences fatigue, weakness, irritability, nervousness, lability, and anorexia, which could easily be confused with an idiopathic anxiety disorder. The psychiatric findings of hyperparathyroidism are well established, as is the favorable prognosis usually associated with correction of the underlying endocrine/metabolic disturbance. Surgical intervention is frequently the treatment of choice, with the most common etiology being a parathyroid adenoma.
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Calcium
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The association between a disturbed calcium balance with hypercalcemia in hyperparathyroidism and psychiatric manifestations is well known, but the type of emotional disturbance is notably nonspecific. A wide variety of encephalopathic, mood or anxiety disorders, and psychotic features are described. Severity of symptoms may be specifically related to the height of the serum calcium level and also to the rapidity of change in electolyte concentration.3,10 An alternate hypothesis is that the prominence of mental status alteration is not correlated to the degree of hypercalcemia; symptoms may be related to a number of factors, which include premorbid adjustment, sociocultural background, and also the interaction between calcium ion and brain functioning.10
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Magnesium
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Hypomagnesemia also occurs in association with hyperparathyroidism, but usually only as sequelae of surgical parathyroid adenoma removal.3 A relationship between psychiatric aspects of central nervous system change and magnesium deficiency has been observed. Metabolic studies revealed a possible negative magnesium balance in hyperparathyroidism, which was presumably due to mobilization of magnesium from bone and increased urinary excretion.3,10 Skeletal demineralization and loss of magnesium may not be directly caused by calcium mobilization and excretion, but is rather a direct effect of parathyroid hormone on the magnesium ion itself.3 Delirium with psychosis is a common presentation in hypomagnesemia, and is difficult to treat without prompt magnesium replacement.3 Other reports of hypomagnesemia emphasize neuropsychiatric symptoms, particularly deficits in spatial conceptualization and also the well-known manifestations of heightened neuromuscular irritability (e.g., Chvostek's or Trousseau's sign).10 Hallucinations are predominantly visual, and a systematized paranoid delusional psychosis is occasionally observed as well.
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ILLUSTRATIVE CASES
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Clinical Vignette No. 1. A 29-year-old, white male treated with lithium was hospitalized on a psychlatric service in a psychotic state with complaints of auditory hallucinations, paranoid delusions, angry outbursts, irritability, and confusion. Serum calcium level on admission was 14.3 mg/dL, which declined to 11.5 after lithium was discontinued. An endocrine evaluation documented that the PTH was elevated at 96.5 pmol/L. Ultrasound of the parathyroid area revealed the presence of adenomata located at both inferior glands. He was transferred to surgery for parathyroid resection. The calcium level, after removal of the adenomata, stabilized at 10.7 mg/dL. He was discharged with mood stability and no psychotic symptoms. Mental status was dramatically improved to normalcy after surgical intervention.
Clinical Vignette No. 2 A 56-year-old white female was admitted to a psychiatric hospital because of depression and a suicide attempt by self-induced skin laceration. She clearly evidenced a mood disorder, and fluoxetine was prescribed. No other psychopathology was noted. Serum calcium levels were 12.5 and 15.8 mg/dL. A parathyroid hormone concentration was significantly abnormal at 286.9 pmol/L and was consistent with hyperparathyroidism. A scintigram was compatible with right thyroid-gland multinodular goiter and inability to rule out a parathyroid disease. Surgically, a parathyroid mass was found and excised; pathology reported it as a parathyroid adenoma. Postoperative recovery was without complications. Two subsequent calcium assays were 8.6 and 9.2 mg/dL. This patient was discharged, with no further manifestation of emotional lability, suicidal thoughts, or depression.
Clinical Vignette No. 3 A 50-year-old white female was hospitalized in a psychiatric facility for acutely disruptive behavior and depression. She evidenced worsening psychotic and mood disorder symptoms, beyond her usual chronic mental illness. Calcium concentrations were 10.6 mg/dL on two determinations; a PTH level was slightly elevated at 93 pmol/L. A subsequent evaluation with a parathyroid scintigram reflected a left-parathyroid adenoma. Surgical resection was uncomplicated, and electrolyte concentrations normalized. Her mental status greatly improved postoperatively, back to her usual baseline level of functioning.
Clinical Vignette No. 4 A 56-year-old white female was followed as an outpatient for several years because of anxiety and depression. Treatment with fluoxetine had been somewhat efficacious, particularly in alleviating depressive symptomatology, but left continued anxiety, somatic concerns, lethargy, and irritability. At one point, she sustained a right humerus fracture, resultant from only minimal trauma. Radiologic evaluation revealed both the fracture and profound osteoporosis. Calcium assays were between 11.4 and 12.7 mg/dL. The parathyroid hormone level was 128 pmol/L. A parathyroid adenoma was suspected on an imaging study. Subsequent to parathyroidectomy with a pathological diagnosis of an adenoma, she experienced a dramatic remission in symptomatology. Antidepressant therapy was no longer needed. Calcium levels became normal. Function and mental status returned to her previous well level of unimpaired performance, free of any psychiatric disorder.
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HYPOPARATHYROIDISM
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Hypoparathyroidism is another endocrinopathy with prominent emotional implications and electrolyte alterations.2 It can be induced iatrogenically after endocrine surgery, or in idiopathic versions, and even in pseudohypoparathyroidism. The latter condition does not relate to parathormone deficiency, but rather to disease-induced unresponsiveness of target organs (i.e., bone and kidney).4 It has been estimated that at least one-half of the postoperative cases with secondary hypoparathyroidism exhibit psychiatric symptoms. Expect to observe low-serum calcium and magnesium levels and an elevated phosphate assay. PTH values should be low. The most common picture is one of delirium.11 Cognitive impairment, psychosis, depression, or anxiety is also frequently observed.
In a large 1962 review of 268 hypoparathyroid cases, about 39% demonstrated cognitive impairment, with nearly 12% evidencing neurotic symptoms, 11% having psychoses, and 21% exhibiting nonspecific psychiatric presentations.12 Symptomatology is more acute and overt in instances of surgically induced cases. This extensive study dominates the literature on psychiatric aspects of hypoparathyroidism; there is a dearth of significant citations otherwise.
Electrolyte replacement sometimes provides symptomatic improvement. Hypomagnesemia may be a cause of psychiatric disturbance in hypoparathyroidism and might be a contributing factor to treatment resistance in psychotic conditions. Examining electrolyte determinations of both of the cations may be diagnostically helpful in some patients who exhibit suboptimal responses to otherwise appropriate therapies.
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Therapy
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Treatment with vitamin D and its analog, calciferol, is frequently prescribed; however, the use of psychotropic medications for related, coexisting mental manifestations is less well clarified. One report offered clinical data suggesting that supplying vitamin D and calcium supplements may not be the optimal therapy in correcting the calcium disturbance in individuals also exhibiting hypomagnesemia.11 The occurrence of psychotic episodes while normocalcemic in hypoparathyroidism implies that a low serum calcium level is not the only factor responsible for producing psychosis. This is particularly true for idiopathic hypoparathyroidism. Psychotic episodes associated with a low calcium level did not respond to correction of hypocalcemia with ergocalciferol (i.e., activated ergosterol, calciferol, and vitamin D) and large doses of antipsychotic medication, until the coexisting hypomagnesemia was resolved.11
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CONCLUSION
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Obtaining a serum calcium level is a necessary and minimal standard as a part of the diagnostic screening evaluation in psychiatric presentations. Examining electrolyte determinations of divalent cations may also be diagnostically helpful for some persons who exhibit a suboptimal response to otherwise appropriate mental illness treatment. Confirmed abnormalities mandate careful, further workup to rule out parathyroid diseases, for which very specific endocrine or surgical therapies are required.
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ACKNOWLEDGMENTS
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The authors thank Sunil Nair, M.D., and Irfan Afaq, M.D., for technical assistance in manuscript revision and Dong Joon Chung, M.D., for editorial service.
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REFERENCES
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Cryer P, Slone R, Whyte M, et al: Depression and hypercalcemia. Clinicopathologic Conference. Am J Med 1996; 101:111–117[Medline]
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Isselbacher K, Braunwald E, Petersdorf, R, et al (eds): Parathyroid-Related Hypercalcernia, 2152 & Hereditary Hypoparathyroidism, 2166. Harrison's Principles of Internal Medicine, 13th Edition. New York, McGraw, 1994
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Jacobs KJ, Merritt CR: Magnesium deficiency in hyperparathyroidism: case report of toxic psychosis. Ann Surg 1966; 162:260–262
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Geffken G, Ward H, Staab JP, et al: Psychiatric morbidity in endocrine disorders. Psychiatr Clin North Am 1998; 21:473–489[Medline]
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Solomon BL, Schaaf M, Smallridge RC: Psychologic symptoms before and after parathyroid surgery. Am J Med 1994; 96:101–106[Medline]
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Karpati G, Frame B: Neuropsychiatric disorders in primary hyperparathyroidism. Arch Neurol 1964; 10:387–397
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Petersen P: Psychiatric disorders in primary hyperparathyroidism. J Clin Endocrinol Metab 1968; 28:1491–1495
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Brown GG, Preisman RC, Klukopee M: Neurobehavioral symptoms in mild primary hyperparathyroidism related to hypercalcemia but not improved by parathyroidectomy. Henry Ford Hospital Medical Journal 1987; 35:211–215 [Medline]
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Feldman F, Mitchell W, Soll S: Psychosis, Cushing's syndrome and hyperparathyroidism. Can Med Assoc J 1968; 98:508–511 [Medline]
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Alarcon RD, Franceschini JA: Hyperparathyroidism and paranoid psychosis: case report and eeview of the literature. Br J Psychiatry 1984; 145:477–486[Abstract/Free Full Text]
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Wee-Kiat A, Ko SM, Tan CH: Calcium, magnesium, and psychotic symptoms in a girl with idiopathic hypoparathyroidism. Psychosom Med 1995; 57:299–302[Abstract/Free Full Text]
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ABSTRACT
INTRODUCTION
