Cushing’s disease in a 15-year-old boy, manifesting in prepubertal age

Abstract

Cushing's disease (CD) is the leading form (75-80%) of the endogenous hypercortisolism (EH) in adolescents. Despite the obvious clinical manifestations, the diagnosis of CD is complicated because of the need of several research methods, the risk of false-positive and false-negative results, difficulties in interpretation and the low percentage of MR-imaging in children. The present patient had noted excessive weight gain since the age of 10 years, a decrease in growth rate was detected retrospectively, absolute short stature developed by the age of 14.5 years. An examination at the age of 15 revealed an inversion of the circadian cortisol rhythm (9:00 378.4 nmol/l, 23:00 598.9 nmol/l), an increase in the cortisol level in saliva at 23:00 (20.32 nmol/l) and excretion in urine (981.5 mcg/day). The overnight dexamethasone test (ODT) was positive (cortisol 44.26 nmol/l), ACTH was in the "gray zone" (22.19 pg/ml). MRI with contrast showed signs of a heterogeneous pituitary gland structure. When patient was re-examined at 15.5 years the inversion of the circadian rhythm of cortisol was accompanied by absolute hypercortisolemia (9:00 843.4 nmol/l, 23:00 929.4 nmol/l), ODT became negative (cortisol 235 nmol/l), ACTH level remained in the "gray zone" (25.1 pg/ml). MRI with contrast showed pituitary adenoma 6×4 mm. An ACTH level gradient between the left inferior petrosal sinus and peripheral blood of 13.3 confirmed CD. After transsphenoidal adenomectomy, a cortisol level of 39.4 nmol/l indicated remission with a low risk of relapse; subsequently a reverse development of EH symptoms were noted. Postoperative diabetes insipidus and primary hypothyroidism required replacement therapy.