Depressive state due to isolated adrenocorticotropic hormone deficiency underlies school refusal

SCHOOL REFUSAL OCCURS in 1% of all school children and adolescents worldwide; it refers to a condition in which children refuse to attend school for reasons of emotional distress.1 School refusal has deleterious effects on academic performance, family bonds and peer relationships.2 In the current case, we diagnosed an adolescent boy who had school refusal with isolated adrenocorticotropic hormone (ACTH) deficiency (IAD), and we successfully treated him with exogenous steroids. The boy lost his father at age 12, during the spring of his first year of middle school, and became severely depressed. He began to refuse to go to school 8 months later. He managed to graduate from middle school and attend high school. However, throughout high school, he was consistently absent from school for 3 months, from spring to summer, which seems like an anniversary effect of his father's death. At age 19, he appeared to be suffering from a severe depressive state with anhedonia and apathy. He was diagnosed with recurrent depressive disorder (DSM-IV 296) with a seasonal pattern and started receiving standard treatment with paroxetine initially at 10 mg and then continuously at 40 mg for 8 weeks. However, this treatment failed to improve his symptoms. We decided to carry out laboratory testing to identify any physical abnormalities contributing to the patient's symptoms. The results showed that his serum ACTH level was strikingly low (6.2 pg/mL, normal range: 8.2–54.8 pg/mL) and his serum cortisol level was also at the lower end of the normal range (5.2 g/dL, normal range: 4.6–19.4 g/dL), though hypoglycemia was not observed (110 mg/dL, normal range: 70–110 mg/dL). After more detailed examinations, including corticotrophin-releasing hormone stimulation test, insulin tolerance test and ACTH stimulation test, we diagnosed him with IAD and began hormone replacement therapy with oral administration of hydrocortisone 10–20 mg/day. His depressive symptoms were completely ameliorated within 1 week without adverse effects. In 2 weeks he returned to high school, enrolled in college, and then continued to attend school every day for subsequent years. Generally, patients with IAD manifest non-specific symptoms, such as asthenia, anorexia and tendency to hypoglycemia. IAD may easily be confounded with major depressive disorder due to similar symptoms of fatigue, lethargy and other signs of adrenal dysfunction; however, patients with IAD fare relatively well during periods of low stress.3 There was a seasonality in his depressive states from spring to summer, which seemed to be related to the anniversary of his father's death. Generally, cortisol-deficit symptoms worsen under stressful conditions because of a relative inability to increase cortisol in response to stress in individuals with IAD. In this case, the anniversary of his father's death might be a stressful event for him, leading to depressive symptoms due to the relative lack of cortisol in response to the strong stressor. Our case suggests that, in treatment-resistant cases of depression, it may be helpful to conduct laboratory testing, including assessment of serum level of ACTH and cortisol. Endocrine-psychiatric syndromes should be taken into consideration, especially if patients demonstrate certain symptoms like lack of motivation, depressed mood, or disturbance of biological periodicity. The patient and his mother gave the authors informed consent to publish this letter.