Psychosomatics 39:176-177, April 1998
© 1998 The Academy of Psychosomatic Medine
Behavioral Changes and Affective Instability Associated With Adult-Onset Adrenoleukodystrophy
Raphael J. Leo, M.D., Department of Psychiatry, School of Medicine and Biomedical Sciences, State University of New York at Buffalo
Key Words: Letter
TO THE EDITOR: A patient with adrenal insufficiency is described who, although well controlled and frequently monitored, presented with marked behavior and mood changes. The psychiatric disturbances prompted evaluation, leading to the diagnosis of adult-onset adrenoleukodystrophy (ALD).
Case Report
A 42-year-old man with a 12-year history of Addison's disease but no psychiatric history was hospitalized because of mild hyponatremia, which was corrected with florinef (0.1 mg) and prednisone (7.5 mg qd). Over the preceding 3 months, he was increasingly "moody," irritable, unusually withdrawn, and impulsive. Although there was no prior history of violence, he was recently prone to unprovoked aggression. The patient had not consumed alcohol or illicit substances. He lost his contracting job because of frequent absences, impulsivity, and decreased ability to complete work.
The patient admitted to depression, reduced sleep, and reduced appetite. He displayed apathy regarding his erratic behavior, although his affect was labile. His speech was clear but monotonous. He lacked spontaneity, responding only with one- or two-word answers. Responses were often delayed. He denied suicidal or homicidal intent and any delusions or hallucinations. He was alert and was oriented to person, place, and time. Performance on tasks of concentration were slow and deliberate. His short-term recall, calculation, abstraction, judgment, and insight were impaired.
Physical examination was notable for hyperpigmentation of the skin and the presence of "new" frontal release signs, that is, jaw jerk, snout reflex, brisk reflexes, and Babinski signs bilaterally. Cranial nerves, motor and sensory modalities, and gait were intact.
Magnetic resonance imaging (MRI) demonstrated extensive bihemispheric white matter lesions involving the frontal lobes, especially on the right, the corpus callosum, the internal capsule, and the parietotemporal regions. After contrast-medium administration, rim enhancement was notable, suggesting a demyelinating process. No masses or intracranial shifting were observed. Urinary arylsulfatase A enzyme levels were normal (10.1 u/L). Serum assays of very long chain fatty acids (VLCFA) revealed elevations in multiple fatty acids (myristate, palmitoleate, oleate acids), suggesting ALD.
Valproic acid was initiated and effectively regulated his affective instability and irritability. Over the ensuing 9 months, his dementia worsened. He developed dysarthria, dysphagia, spastic paresis, ataxia, and incontinence. He was readmitted for comfort measures and died shortly thereafter.
Discussion
This case illustrates that new-onset psychiatric symptoms should be investigated for organic causes, even if the patient has a known medical condition. Although the patient was hyponatremic on admission, he was not in Addisonian crisis. The behavior changes, cognitive decline, and neurologic symptoms suggested that a progressive disorder was under way, of which Addison's disease was a part. In patients with Addison's disease, diagnosis of ALD is suggested by the abrupt development of neuropsychiatric symptoms, associated with MRI confirmation of extensive, usually symmetric, white matter disease.
Most commonly, patients with ALD present in childhood. Impaired VLCFA metabolism results in excessive VLCFA accumulation within the adrenal gland and white matter of the nervous system.1,2 Hence, progressive neuroendocrinologic disturbances often appear in the first decade, and death ensues within years. Onset of ALD in adulthood is rare. The progression of the disorder is slower, and symptoms can be variable. Neurologic symptoms include visual field deficits, dysarthria, ataxia, and spasticity. Adrenal symptoms include lethargy, orthostasis, nausea, and skin hyperpigmentation. It is possible, as in this case, for patients to have a long history of adrenal insufficiency before neuropsychiatric symptoms manifest.3 By contrast, other affected adults lacked history of significant adrenal dysfunction.4 Hence, diagnosis of ALD in adulthood based upon clinical symptoms alone can be difficult.
Psychiatric symptoms can appear at varying points in disease progression. Symptoms can include concentration deficits and dementia, mood disturbances, psychosis, and personality changes.4,5 Misdiagnosis of "functional" psychiatric disorders has occurred, particularly if the psychiatric symptoms dominate the early course of the disorder.3,5,6
In this case, diagnosis of ALD was strongly supported by symptoms, disease progression, MRI findings, and elevated VLCFAs. Metachromatic leukodystrophy was ruled out by normal levels of urinary arylsulfatase A. The predominant frontal-lobe involvement, as observed here, is unusual in ALD. Nonetheless, other reports demonstrated variable central nervous system involvement in adult-onset ALD (e.g., presenting as Balint's syndrome7 or Kluver-Bucy syndrome8).
Treatment is symptomatic, for example, steroid use for adrenal insufficiency and psychotropics for psychiatric symptoms. Measures to control disease progression with dietary VLCFA restriction, or use of agents increasing VLCFA intracellular metabolism, fail to arrest the neurolgic deterioration in ALD.2 As ALD is an X-linked recessive disorder,2,9 genetic counseling of family members may be advisable.
Although rare, ALD may present in adulthood. The emergence of neuropsychiatric symptoms in a patient with a prior history of Addison's disease should prompt evaluation for this disorder.
REFERENCES
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