Low dose mitotane-induced neurological and endocrinological complication in a 5-year-old girl with adrenocortical carcinoma.

Mitotane is an adrenolytic drug that exhibits a therapeutic effect within a narrow target range (14-20 μg/dL). Various complications develop if the upper limit is exceeded. We present the case of a 5-year-old girl with breast development, acne, and pubic hair; she was diagnosed with an adrenal mass that was then excised. The Pathological result was adrenocortical carcinoma with a high risk of malignancy, and adjuvant therapy (combined mitotane and radiation therapy) was commenced. Mitotane was initiated at a low dose to allow monitoring of the therapeutic drug level, and high-dose hydrocortisone was also commenced. However, the patient showed elevated adrenocorticotropic hormone levels and vague symptoms such as general weakness and difficulty in concentration. It was important to determine if these symptoms were signs of the neurological complications that develop when mitotane levels are elevated. Encephalopathy progression and pubertal signs appeared 6 months after diagnosis, induced by elevated mitotane levels. The mitotane levels decreased to sub-therapeutic levels several months after discontinuation of mitotane, at which time endocrinopathy (central hypothyroidism, hypercholesterolemia, and secondary central precocious puberty) also developed. The case shows that low-dose mitotane can trigger neurological and endocrinological complications in a pediatric patient; the drug dose should be individualized with frequent monitoring of the therapeutic level.